7-100107362-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.499
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 id is 2620878.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TAF6NM_139315.3 linkuse as main transcriptc.1918G>A p.Gly640Ser missense_variant 15/15 ENST00000453269.7
AP4M1NM_004722.4 linkuse as main transcriptc.*480C>T 3_prime_UTR_variant 15/15 ENST00000359593.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TAF6ENST00000453269.7 linkuse as main transcriptc.1918G>A p.Gly640Ser missense_variant 15/151 NM_139315.3 P1P49848-1
AP4M1ENST00000359593.9 linkuse as main transcriptc.*480C>T 3_prime_UTR_variant 15/151 NM_004722.4 P3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
32
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
GnomAD3 exomes
AF:
0.0000226
AC:
5
AN:
221678
Hom.:
0
AF XY:
0.0000420
AC XY:
5
AN XY:
119094
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 SAS exome
AF:
0.000121
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000198
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000846
AC:
12
AN:
1418844
Hom.:
0
Cov.:
34
AF XY:
0.0000100
AC XY:
7
AN XY:
700342
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000869
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000460
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsSep 08, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
7.7
DANN
Benign
0.60
DEOGEN2
Benign
0.032
T;.;T;T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.64
.;T;.;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.040
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.20
N;.;N;N;.
MutationTaster
Benign
1.0
D;N;N;N;N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
0.27
N;N;N;N;N
REVEL
Benign
0.038
Sift
Benign
0.19
T;T;T;T;T
Sift4G
Benign
0.78
T;T;T;T;T
Polyphen
0.0010
B;.;B;B;.
Vest4
0.13
MutPred
0.22
Gain of phosphorylation at G640 (P = 0.0113);.;Gain of phosphorylation at G640 (P = 0.0113);Gain of phosphorylation at G640 (P = 0.0113);.;
MVP
0.30
MPC
0.43
ClinPred
0.026
T
GERP RS
2.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.027
gMVP
0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs202159425; hg19: chr7-99704985; API