chr7-100106825-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_004722.4(AP4M1):c.1305C>T(p.Asn435Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 1,613,992 control chromosomes in the GnomAD database, including 834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 44 hom., cov: 32)

Exomes 𝑓: 0.030 ( 790 hom. )

Consequence

AP4M1
NM_004722.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.27

Publications

9 publications found

Variant links:

Genes affected

AP4M1 (HGNC:574): (adaptor related protein complex 4 subunit mu 1) This gene encodes a subunit of the heterotetrameric AP-4 complex. The encoded protein belongs to the adaptor complexes medium subunits family. This AP-4 complex is involved in the recognition and sorting of cargo proteins with tyrosine-based motifs from the trans-golgi network to the endosomal-lysosomal system. [provided by RefSeq, Jul 2008]

AP4M1 links:

TAF6 (HGNC:11540): (TATA-box binding protein associated factor 6) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes one of the smaller subunits of TFIID that binds weakly to TBP but strongly to TAF1, the largest subunit of TFIID. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

TAF6 Gene-Disease associations (from GenCC):

Alazami-Yuan syndrome
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TAF6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.1).

BP6

Variant 7-100106825-C-T is Benign according to our data. Variant chr7-100106825-C-T is described in ClinVar as Benign. ClinVar VariationId is 128404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.27 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0184 (2800/152344) while in subpopulation NFE AF = 0.0299 (2031/68030). AF 95% confidence interval is 0.0288. There are 44 homozygotes in GnomAd4. There are 1333 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP4M1	NM_004722.4 link	c.1305C>T	p.Asn435Asn	synonymous_variant	Exon 15 of 15	ENST00000359593.9	NP_004713.2	O00189
TAF6	NM_139315.3 link	c.*421G>A		downstream_gene_variant		ENST00000453269.7	NP_647476.1	P49848-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP4M1	ENST00000359593.9 link	c.1305C>T	p.Asn435Asn	synonymous_variant	Exon 15 of 15	1	NM_004722.4	ENSP00000352603.4		O00189
TAF6	ENST00000453269.7 link	c.*421G>A		downstream_gene_variant		1	NM_139315.3	ENSP00000389575.2		P49848-1

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2802

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00622

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0203

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0299

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.0191

AC:

4794

AN:

251092

AF XY:

0.0204

show subpopulations

Gnomad AFR exome

AF:

0.00573

Gnomad AMR exome

AF:

0.00787

Gnomad ASJ exome

AF:

0.0202

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0150

Gnomad NFE exome

AF:

0.0272

Gnomad OTH exome

AF:

0.0227

GnomAD4 exome

AF:

0.0296

AC:

43296

AN:

1461648

Hom.:

790

Cov.:

AF XY:

0.0296

AC XY:

21519

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.00484

AC:

162

AN:

33480

American (AMR)

AF:

0.00823

AC:

368

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0204

AC:

533

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0246

AC:

2126

AN:

86256

European-Finnish (FIN)

AF:

0.0160

AC:

851

AN:

53186

Middle Eastern (MID)

AF:

0.0165

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0336

AC:

37392

AN:

1112004

Other (OTH)

AF:

0.0292

AC:

1766

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

2908

5816

8723

11631

14539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1460

2920

4380

5840

7300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0184

AC:

2800

AN:

152344

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1333

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00620

AC:

258

AN:

41598

American (AMR)

AF:

0.00837

AC:

128

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0245

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0201

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0135

AC:

143

AN:

10630

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0299

AC:

2031

AN:

68030

Other (OTH)

AF:

0.0137

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

146

292

439

585

731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0254

Hom.:

131

Bravo

AF:

0.0179

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0308

EpiControl

AF:

0.0286

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 01, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 01, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hereditary spastic paraplegia

Benign:1

Nov 27, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hereditary spastic paraplegia 50

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.9

(source)

DANN

Benign

0.88

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over