1-222561388-C-T

Variant names:

• chr1-222561388-C-T
• NM_005681.4:c.1216G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005681.4(TAF1A):​c.1216G>A​(p.Val406Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF1A NM_005681.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1A	NM_005681.4	c.1216G>A	p.Val406Met	missense_variant	Exon 10 of 11	ENST00000352967.9	NP_005672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1A	ENST00000352967.9	c.1216G>A	p.Val406Met	missense_variant	Exon 10 of 11	1	NM_005681.4	ENSP00000327072.6
TAF1A	ENST00000350027.8	c.1216G>A	p.Val406Met	missense_variant	Exon 10 of 12	2		ENSP00000339976.4
TAF1A	ENST00000366890.5	c.874G>A	p.Val292Met	missense_variant	Exon 9 of 11	2		ENSP00000355856.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1216G>A (p.V406M) alteration is located in exon 10 (coding exon 9) of the TAF1A gene. This alteration results from a G to A substitution at nucleotide position 1216, causing the valine (V) at amino acid position 406 to be replaced by a methionine (M). 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	Uncertain	0.39
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	.;T;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.87	D;T;.
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.6	.;M;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.70
MutPred		0.25		.;Loss of catalytic residue at V406 (P = 0.0064);Loss of catalytic residue at V406 (P = 0.0064);
MVP		0.44
MPC		0.89
ClinPred		0.90	D
GERP RS		4.9
Varity_R		0.13
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-222734730;