Genetic Variant NM_005681.4:c.294T>G (chr1-222579870-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005681.4(TAF1A):c.294T>G(p.Ile98Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 1,601,684 control chromosomes in the GnomAD database, including 281 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.024 ( 148 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 133 hom. )

Consequence

TAF1A
NM_005681.4 missense, splice_region

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0870

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021394193).

BP6

Variant 1-222579870-A-C is Benign according to our data. Variant chr1-222579870-A-C is described in ClinVar as [Benign]. Clinvar id is 785952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1A	NM_005681.4 link	c.294T>G	p.Ile98Met	missense_variant, splice_region_variant	Exon 4 of 11	ENST00000352967.9	NP_005672.1	Q15573-1B4DS21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1A	ENST00000352967.9 link	c.294T>G	p.Ile98Met	missense_variant, splice_region_variant	Exon 4 of 11	1	NM_005681.4	ENSP00000327072.6		Q15573-1

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3661

AN:

152162

Hom.:

149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0843

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00607

AC:

1444

AN:

237770

Hom.:

AF XY:

0.00448

AC XY:

576

AN XY:

128476

show subpopulations

Gnomad AFR exome

AF:

0.0830

Gnomad AMR exome

AF:

0.00311

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000151

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000127

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00239

AC:

3462

AN:

1449404

Hom.:

133

Cov.:

AF XY:

0.00208

AC XY:

1495

AN XY:

720402

show subpopulations

Gnomad4 AFR exome

AF:

0.0875

Gnomad4 AMR exome

AF:

0.00356

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000145

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000956

Gnomad4 OTH exome

AF:

0.00544

GnomAD4 genome

AF:

0.0241

AC:

3666

AN:

152280

Hom.:

148

Cov.:

AF XY:

0.0232

AC XY:

1726

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0842

Gnomad4 AMR

AF:

0.00849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.00295

Hom.:

Bravo

AF:

0.0278

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0758

AC:

334

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00728

AC:

884

Asia WGS

AF:

0.00462

AC:

AN:

3474

EpiCase

AF:

0.00

EpiControl

AF:

0.000415

ClinVar

Significance: 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: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0097

T;T

Eigen

Benign

0.078

Eigen_PC

Benign

0.071

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.59

T;.

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.069

Sift

Benign

0.10

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.73

P;P

Vest4

0.17

MVP

0.35

MPC

0.56

ClinPred

0.021

GERP RS

3.6

Varity_R

0.078

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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