chr1-222577483-T-G

Variant names:

• chr1-222577483-T-G
• NM_005681.4:c.566A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005681.4(TAF1A):​c.566A>C​(p.Tyr189Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y189F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TAF1A NM_005681.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35259503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1A	NM_005681.4	c.566A>C	p.Tyr189Ser	missense_variant	Exon 5 of 11	ENST00000352967.9	NP_005672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1A	ENST00000352967.9	c.566A>C	p.Tyr189Ser	missense_variant	Exon 5 of 11	1	NM_005681.4	ENSP00000327072.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461672 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.085	.;T;T;.
Eigen	Benign	0.063
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;T;.;D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.7	.;M;M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.26
Sift	Benign	0.25	T;T;T;T
Sift4G	Benign	0.17	T;T;T;.
Polyphen		0.42	.;B;B;.
Vest4		0.66
MutPred		0.55		.;Gain of disorder (P = 0.0132);Gain of disorder (P = 0.0132);.;
MVP		0.49
MPC		0.59
ClinPred		0.62	D
GERP RS		4.5
Varity_R		0.23
gMVP		0.54

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: chr1-222750825; COSMIC: COSV61918179;