Genetic Variant TAF1D:p.Glu137Gln (chr11-93738159-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024116.4(TAF1D):c.409G>C(p.Glu137Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,567,892 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

TAF1D
NM_024116.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17581928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1D	NM_024116.4 link	c.409G>C	p.Glu137Gln	missense_variant	Exon 3 of 6	ENST00000448108.7	NP_077021.1	Q9H5J8A0A024R3A9
TAF1D	NR_146090.2 link	n.610G>C		non_coding_transcript_exon_variant	Exon 3 of 14
TAF1D	NR_146091.2 link	n.610G>C		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.409G>C	p.Glu137Gln	missense_variant	Exon 3 of 6	5	NM_024116.4	ENSP00000410409.2		Q9H5J8

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000958

AC:

AN:

208704

AF XY:

0.00000877

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000197

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000848

AC:

AN:

1415758

Hom.:

Cov.:

AF XY:

0.0000128

AC XY:

AN XY:

703658

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30452

American (AMR)

AF:

0.00

AC:

AN:

29922

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23518

East Asian (EAS)

AF:

0.00

AC:

AN:

38912

South Asian (SAS)

AF:

0.00

AC:

AN:

77844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5514

European-Non Finnish (NFE)

AF:

0.0000109

AC:

AN:

1099256

Other (OTH)

AF:

0.00

AC:

AN:

58206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000870

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 14, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.409G>C (p.E137Q) alteration is located in exon 3 (coding exon 2) of the TAF1D gene. This alteration results from a G to C substitution at nucleotide position 409, causing the glutamic acid (E) at amino acid position 137 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.95

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.69

M_CAP

Benign

0.0077

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.8

PhyloP100

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.4

REVEL

Benign

0.096

Sift

Benign

0.13

Sift4G

Benign

0.25

Polyphen

0.32

Vest4

0.21

MutPred

0.64

Gain of MoRF binding (P = 0.07);

MVP

0.31

MPC

0.23

ClinPred

0.11

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.087

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-93738159-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over