Genetic Variant TAF1D:p.Ala144Ser (chr11-93738138-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024116.4(TAF1D):c.430G>T(p.Ala144Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,410,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

TAF1D
NM_024116.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.539

Publications

2 publications found

Variant links:

Genes affected

TAF1D (HGNC:28759): (TATA-box binding protein associated factor, RNA polymerase I subunit D) TAF1D is a member of the SL1 complex, which includes TBP (MIM 600075) and TAF1A (MIM 604903), TAF1B (MIM 604904), and TAF1C (MIM 604905), and plays a role in RNA polymerase I transcription (Wang et al., 2004 [PubMed 15520167]; Gorski et al., 2007 [PubMed 17318177]).[supplied by OMIM, Jun 2009]

TAF1D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065695256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1D	NM_024116.4 link	c.430G>T	p.Ala144Ser	missense_variant	Exon 3 of 6	ENST00000448108.7	NP_077021.1	Q9H5J8A0A024R3A9
TAF1D	NR_146090.2 link	n.631G>T		non_coding_transcript_exon_variant	Exon 3 of 14
TAF1D	NR_146091.2 link	n.631G>T		non_coding_transcript_exon_variant	Exon 3 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1D	ENST00000448108.7 link	c.430G>T	p.Ala144Ser	missense_variant	Exon 3 of 6	5	NM_024116.4	ENSP00000410409.2		Q9H5J8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000145

AC:

AN:

206772

AF XY:

0.00000885

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000130

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000425

AC:

AN:

1410364

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

700014

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30434

American (AMR)

AF:

0.00

AC:

AN:

29528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23252

East Asian (EAS)

AF:

0.0000514

AC:

AN:

38892

South Asian (SAS)

AF:

0.0000388

AC:

AN:

77318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51832

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5476

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095662

Other (OTH)

AF:

0.0000173

AC:

AN:

57970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 03, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.430G>T (p.A144S) alteration is located in exon 3 (coding exon 2) of the TAF1D gene. This alteration results from a G to T substitution at nucleotide position 430, causing the alanine (A) at amino acid position 144 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.8

(source)

DANN

Benign

0.72

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.20

M_CAP

Benign

0.0046

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.54

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.48

REVEL

Benign

0.019

Sift

Benign

0.12

Sift4G

Benign

0.39

Polyphen

0.48

Vest4

0.12

MutPred

0.31

Gain of disorder (P = 0.0269);

MVP

0.099

MPC

0.095

ClinPred

0.026

GERP RS

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.097

gMVP

0.18

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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11-93738138-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over