7-100107269-C-T

Position:

chr7-100107269-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_139315.3(TAF6):c.2011G>A(p.Gly671Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,523,096 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 19 hom. )

Consequence

TAF6
NM_139315.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.161

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041299164).

BP6

Variant 7-100107269-C-T is Benign according to our data. Variant chr7-100107269-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 781652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF6	NM_139315.3 linkuse as main transcript	c.2011G>A	p.Gly671Ser	missense_variant	15/15	ENST00000453269.7
AP4M1	NM_004722.4 linkuse as main transcript	c.*387C>T		3_prime_UTR_variant	15/15	ENST00000359593.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF6	ENST00000453269.7 linkuse as main transcript	c.2011G>A	p.Gly671Ser	missense_variant	15/15	1	NM_139315.3	P1	P49848-1
AP4M1	ENST00000359593.9 linkuse as main transcript	c.*387C>T		3_prime_UTR_variant	15/15	1	NM_004722.4	P3

Frequencies

GnomAD3 genomes

AF:

0.00328

AC:

499

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00413

Gnomad OTH

AF:

0.00814

GnomAD3 exomes

AF:

0.00367

AC:

651

AN:

177194

Hom.:

AF XY:

0.00381

AC XY:

357

AN XY:

93702

show subpopulations

Gnomad AFR exome

AF:

0.000480

Gnomad AMR exome

AF:

0.00743

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000680

Gnomad FIN exome

AF:

0.000593

Gnomad NFE exome

AF:

0.00450

Gnomad OTH exome

AF:

0.00470

GnomAD4 exome

AF:

0.00416

AC:

5702

AN:

1370784

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

2835

AN XY:

672532

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00695

Gnomad4 ASJ exome

AF:

0.0204

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00102

Gnomad4 FIN exome

AF:

0.000703

Gnomad4 NFE exome

AF:

0.00428

Gnomad4 OTH exome

AF:

0.00535

GnomAD4 genome

AF:

0.00328

AC:

499

AN:

152312

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

229

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.0207

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00413

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00441

Hom.:

Bravo

AF:

0.00364

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000459

AC:

ESP6500EA

AF:

0.00514

AC:

ExAC

AF:

0.00341

AC:

405

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	AP4M1: BS2; TAF6: BP4, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 15, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

T;.;T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.69

.;T;.;T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.0041

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.;N;N;.

MutationTaster

Benign

0.87

D;N;N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.040

N;N;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.12

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.47

P;.;P;P;.

Vest4

0.15

MVP

0.27

MPC

0.47

ClinPred

0.0080

GERP RS

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.037

gMVP

0.15

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over