1-222569623-T-G

Position:

chr1-222569623-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000352967.9(TAF1A):c.781A>C(p.Thr261Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

TAF1A
ENST00000352967.9 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.75

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:

TAF1A (HGNC:):

TAF1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04009512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF1A	NM_005681.4 linkuse as main transcript	c.781A>C	p.Thr261Pro	missense_variant	7/11	ENST00000352967.9	NP_005672.1	Q15573-1B4DS21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF1A	ENST00000352967.9 linkuse as main transcript	c.781A>C	p.Thr261Pro	missense_variant	7/11	1	NM_005681.4	ENSP00000327072.6		Q15573-1

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.000111

AC:

AN:

251178

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1461726

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000328

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000722

Hom.:

Bravo

AF:

0.000370

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cardiomyopathy, familial restrictive, 6

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Columbia University Laboratory of Personalized Genomic Medicine, Columbia University Medical Center

Sep 19, 2022

TAF1A encodes a TATA box-binding protein-associated factor which is required for RNA polymerase I to synthesize ribosomal RNA. The c.781A>C, p.Thr261Pro variant in the TAF1A gene is a maternally inherited missense variant, which results in a substitution of threonine residue to proline at position 261/451 of the protein. This variant is rare from the gnomAD database with allele frequency 0.0001415 (40/282588 heterozygotes, 0 homozygote) indicating that it is not a common benign occurrence in the populations represented in the database. To the best of our knowledge, the variant c.781A>C, p.Thr261Pro in TAF1A has not been reported in any affected individual. . In silico prediction MutationTaster, Provean, and SIFT prediction softwares predicting this variant to be disease causing, damaging, and damaging, respectively. Based on these findings, and using the ACMG variant classification guidelines (Richards et al. Genet Med. 2015), this variant has been classified as variant of unknown significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

.;T;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.73

T;T;.;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.040

T;T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.6

.;M;M;.

MutationTaster

Benign

0.70

D;D;D;D;D

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.9

D;D;D;D

REVEL

Benign

0.15

Sift

Benign

0.15

T;T;T;T

Sift4G

Uncertain

0.051

T;D;D;.

Polyphen

0.99

.;D;D;.

Vest4

0.46

MVP

0.61

MPC

0.96

ClinPred

0.10

GERP RS

6.0

Varity_R

0.63

gMVP

0.58

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