Variant rs4150167 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001243156.2(TAF1C):c.1489G>A(p.Gly497Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,595,058 control chromosomes in the GnomAD database, including 443 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 37 hom., cov: 33)

Exomes 𝑓: 0.020 ( 406 hom. )

Consequence

TAF1C
NM_001243156.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.542

Variant links:

Genes affected

TAF1C (HGNC:11534): (TATA-box binding protein associated factor, RNA polymerase I subunit C) Initiation of transcription by RNA polymerase I requires the formation of a complex composed of the TATA-binding protein (TBP) and three TBP-associated factors (TAFs) specific for RNA polymerase I. This complex, known as SL1, binds to the core promoter of ribosomal RNA genes to position the polymerase properly and acts as a channel for regulatory signals. This gene encodes the largest SL1-specific TAF. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2011]

TAF1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025316477).

BP6

Variant 16-84180078-C-T is Benign according to our data. Variant chr16-84180078-C-T is described in ClinVar as [Benign]. Clinvar id is 3068683.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF1C	NM_001243156.2 link	c.1489G>A	p.Gly497Arg	missense_variant	14/15	ENST00000566732.6	NP_001230085.2	Q15572-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF1C	ENST00000566732.6 link	c.1489G>A	p.Gly497Arg	missense_variant	14/15	2	NM_001243156.2	ENSP00000455933.1		Q15572-6

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2393

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00847

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.0427

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0316

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0199

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0194

AC:

4318

AN:

222282

Hom.:

AF XY:

0.0209

AC XY:

2555

AN XY:

122090

show subpopulations

Gnomad AFR exome

AF:

0.00794

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.0409

Gnomad EAS exome

AF:

0.000174

Gnomad SAS exome

AF:

0.0393

Gnomad FIN exome

AF:

0.00455

Gnomad NFE exome

AF:

0.0215

Gnomad OTH exome

AF:

0.0323

GnomAD4 exome

AF:

0.0200

AC:

28790

AN:

1442766

Hom.:

406

Cov.:

AF XY:

0.0207

AC XY:

14872

AN XY:

716934

show subpopulations

Gnomad4 AFR exome

AF:

0.00807

Gnomad4 AMR exome

AF:

0.0136

Gnomad4 ASJ exome

AF:

0.0423

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0372

Gnomad4 FIN exome

AF:

0.00542

Gnomad4 NFE exome

AF:

0.0198

Gnomad4 OTH exome

AF:

0.0219

GnomAD4 genome

AF:

0.0157

AC:

2385

AN:

152292

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1150

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00844

Gnomad4 AMR

AF:

0.0154

Gnomad4 ASJ

AF:

0.0427

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0315

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.0199

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0219

Hom.:

Bravo

AF:

0.0156

TwinsUK

AF:

0.0175

AC:

ALSPAC

AF:

0.0197

AC:

ESP6500AA

AF:

0.00418

AC:

ESP6500EA

AF:

0.0184

AC:

156

ExAC

AF:

0.0184

AC:

2221

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Complex neurodevelopmental disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics, Royal Melbourne Hospital

May 04, 2023

South Asian population allele frequency is 3.735% (rs4150167, 1059/26938 alleles, 75 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.2.1, this variant is classified as BENIGN. Following criteria are met: BA1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

.;.;T;.;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.74

T;T;T;T;.

MetaRNN

Benign

0.0025

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;.;L;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.7

.;N;N;N;N

REVEL

Benign

0.044

Sift

Uncertain

0.0060

.;D;T;T;T

Sift4G

Uncertain

0.030

D;D;D;D;D

Polyphen

0.98, 0.99

.;D;D;D;.

Vest4

0.11

MutPred

0.31

.;.;Gain of solvent accessibility (P = 0.0014);.;.;

ClinPred

0.011

GERP RS

1.3

Varity_R

0.081

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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