1-222561411-G-A

Position:

• chr1-222561411-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005681.4(TAF1A):​c.1193C>T​(p.Ala398Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: TAF1A NM_005681.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.957

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090120465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF1A	NM_005681.4	c.1193C>T	p.Ala398Val	missense_variant	10/11	ENST00000352967.9	NP_005672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF1A	ENST00000352967.9	c.1193C>T	p.Ala398Val	missense_variant	10/11	1	NM_005681.4	ENSP00000327072	P1
TAF1A	ENST00000350027.8	c.1193C>T	p.Ala398Val	missense_variant	10/12	2		ENSP00000339976	P1
TAF1A	ENST00000366890.5	c.851C>T	p.Ala284Val	missense_variant	9/11	2		ENSP00000355856

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.1193C>T (p.A398V) alteration is located in exon 10 (coding exon 9) of the TAF1A gene. This alteration results from a C to T substitution at nucleotide position 1193, causing the alanine (A) at amino acid position 398 to be replaced by a valine (V). 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	0.097
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.0057	.;T;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.77	T;T;.
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.090	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	.;M;M
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.53	N;N;N
REVEL	Benign	0.049
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.23	.;B;B
Vest4		0.27
MutPred		0.25		.;Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.29
MPC		0.28
ClinPred		0.053	T
GERP RS		1.2
Varity_R		0.031
gMVP		0.090

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-222734753;