NM_139315.3:c.1918G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_139315.3(TAF6):c.1918G>A(p.Gly640Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,571,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

TAF6
NM_139315.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.499

Publications

0 publications found

Variant links:

Genes affected

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 links:

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 Gene-Disease associations (from GenCC):

AP-4 deficiency syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hereditary spastic paraplegia 50
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
AP4-related intellectual disability and spastic paraplegia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

AP4M1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040243685).

BP6

Variant 7-100107362-C-T is Benign according to our data. Variant chr7-100107362-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2620878.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139315.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAF6	NM_139315.3	MANE Select	c.1918G>A	p.Gly640Ser	missense	Exon 15 of 15	NP_647476.1	P49848-1
AP4M1	NM_004722.4	MANE Select	c.*480C>T		3_prime_UTR	Exon 15 of 15	NP_004713.2
TAF6	NM_001365004.1		c.2056G>A	p.Gly686Ser	missense	Exon 16 of 16	NP_001351933.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAF6	ENST00000453269.7	TSL:1 MANE Select	c.1918G>A	p.Gly640Ser	missense	Exon 15 of 15	ENSP00000389575.2	P49848-1
TAF6	ENST00000344095.8	TSL:1	c.1918G>A	p.Gly640Ser	missense	Exon 15 of 15	ENSP00000344537.4	P49848-1
TAF6	ENST00000452041.5	TSL:1	c.1918G>A	p.Gly640Ser	missense	Exon 15 of 15	ENSP00000416396.1	P49848-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000226

AC:

AN:

221678

AF XY:

0.0000420

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000198

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000846

AC:

AN:

1418844

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

700342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32398

American (AMR)

AF:

0.00

AC:

AN:

39712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23480

East Asian (EAS)

AF:

0.00

AC:

AN:

39168

South Asian (SAS)

AF:

0.0000869

AC:

AN:

80550

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51880

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

0.00000460

AC:

AN:

1087692

Other (OTH)

AF:

0.00

AC:

AN:

58380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.7

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.032

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.64

M_CAP

Benign

0.016

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

0.50

PrimateAI

Benign

0.42

PROVEAN

Benign

0.27

REVEL

Benign

0.038

Sift

Benign

0.19

Sift4G

Benign

0.78

Polyphen

0.0010

Vest4

0.13

MutPred

0.22

Gain of phosphorylation at G640 (P = 0.0113)

MVP

0.30

MPC

0.43

ClinPred

0.026

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.28

Mutation Taster

=97/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over