Genetic Variant TAF1A:p.Arg435Gln (chr1-222558709-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

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

The NM_005681.4(TAF1A):c.1304G>A(p.Arg435Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0076 in 1,576,986 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 41 hom. )

Consequence

TAF1A
NM_005681.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.06

Variant links:

Genes affected

TAF1A (HGNC:11532): (TATA-box binding protein associated factor, RNA polymerase I subunit A) This gene encodes a subunit of the RNA polymerase I complex, Selectivity Factor I (SLI). The encoded protein is a TATA box-binding protein-associated factor that plays a role in the assembly of the RNA polymerase I preinitiation complex. Alternate splicing results in multiple transcript variants encoding multiple isoforms.[provided by RefSeq, Jan 2011]

TAF1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024210513).

BP6

Variant 1-222558709-C-T is Benign according to our data. Variant chr1-222558709-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 787580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1A	NM_005681.4 link	c.1304G>A	p.Arg435Gln	missense_variant	Exon 11 of 11	ENST00000352967.9	NP_005672.1	Q15573-1B4DS21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAF1A	ENST00000352967.9 link	c.1304G>A	p.Arg435Gln	missense_variant	Exon 11 of 11	1	NM_005681.4	ENSP00000327072.6	Q15573-1
TAF1A	ENST00000350027.8 link	c.1304G>A	p.Arg435Gln	missense_variant	Exon 11 of 12	2		ENSP00000339976.4	Q15573-1
TAF1A	ENST00000366890.5 link	c.962G>A	p.Arg321Gln	missense_variant	Exon 10 of 11	2		ENSP00000355856.1	Q15573-2

Frequencies

GnomAD3 genomes

AF:

0.00548

AC:

833

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00721

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00831

Gnomad OTH

AF:

0.00814

GnomAD3 exomes

AF:

0.00560

AC:

1325

AN:

236516

Hom.:

AF XY:

0.00581

AC XY:

745

AN XY:

128260

show subpopulations

Gnomad AFR exome

AF:

0.000755

Gnomad AMR exome

AF:

0.00468

Gnomad ASJ exome

AF:

0.00885

Gnomad EAS exome

AF:

0.0000573

Gnomad SAS exome

AF:

0.00473

Gnomad FIN exome

AF:

0.000327

Gnomad NFE exome

AF:

0.00842

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00783

AC:

11152

AN:

1424816

Hom.:

Cov.:

AF XY:

0.00791

AC XY:

5599

AN XY:

708004

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00510

Gnomad4 ASJ exome

AF:

0.00973

Gnomad4 EAS exome

AF:

0.0000514

Gnomad4 SAS exome

AF:

0.00504

Gnomad4 FIN exome

AF:

0.000343

Gnomad4 NFE exome

AF:

0.00895

Gnomad4 OTH exome

AF:

0.00751

GnomAD4 genome

AF:

0.00547

AC:

833

AN:

152170

Hom.:

Cov.:

AF XY:

0.00504

AC XY:

375

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00720

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00831

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00794

Hom.:

Bravo

AF:

0.00599

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00840

AC:

ExAC

AF:

0.00624

AC:

757

Asia WGS

AF:

0.00145

AC:

AN:

3450

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.2

DANN

Benign

0.90

DEOGEN2

Benign

0.0036

.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.68

T;T;.

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.47

.;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.21

N;N;N

REVEL

Benign

0.021

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.45

T;T;T

Polyphen

0.012

.;B;B

Vest4

0.085

MVP

0.15

MPC

0.30

ClinPred

0.0048

GERP RS

-3.5

Varity_R

0.030

gMVP

0.083

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