chr1-222558709-C-G

Variant names:

• chr1-222558709-C-G
• NM_005681.4:c.1304G>C

Variant summary

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

The NM_005681.4(TAF1A):​c.1304G>C​(p.Arg435Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,425,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. R435Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TAF1A NM_005681.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=0.11878234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1A	NM_005681.4	c.1304G>C	p.Arg435Pro	missense_variant	Exon 11 of 11	ENST00000352967.9	NP_005672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1A	ENST00000352967.9	c.1304G>C	p.Arg435Pro	missense_variant	Exon 11 of 11	1	NM_005681.4	ENSP00000327072.6
TAF1A	ENST00000350027.8	c.1304G>C	p.Arg435Pro	missense_variant	Exon 11 of 12	2		ENSP00000339976.4
TAF1A	ENST00000366890.5	c.962G>C	p.Arg321Pro	missense_variant	Exon 10 of 11	2		ENSP00000355856.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1425296 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 708244

Gnomad4 AFR exome AF: 0.0000307

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: 0.00

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	0.31
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0047	.;T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.72	T;T;.
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.7	.;L;L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.38	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.87	.;P;P
Vest4		0.46
MutPred		0.31		.;Gain of methylation at K432 (P = 0.0968);Gain of methylation at K432 (P = 0.0968);
MVP		0.41
MPC		0.95
ClinPred		0.73	D
GERP RS		-3.5
Varity_R		0.13
gMVP		0.57

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: chr1-222732051;