rs956228152

Variant names:

• chr1-222584139-C-G
• rs956228152
• NM_005681.4:c.280G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-222584139-C-G
• chr1-222584139-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005681.4(TAF1A):​c.280G>C​(p.Ala94Pro) 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. 15/22 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. A94V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF1A NM_005681.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 0 publications found

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]

TAF1A Gene-Disease associations (from GenCC):

• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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=0.105166376).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005681.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1A	NM_005681.4	MANE Select	c.280G>C	p.Ala94Pro	missense	Exon 3 of 11	NP_005672.1	Q15573-1
	TAF1A	NM_001201536.1		c.280G>C	p.Ala94Pro	missense	Exon 3 of 12	NP_001188465.1	A8K4K5
	TAF1A	NM_139352.2		c.-51-4267G>C		intron	N/A	NP_647603.1	Q15573-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1A	ENST00000352967.9	TSL:1 MANE Select	c.280G>C	p.Ala94Pro	missense	Exon 3 of 11	ENSP00000327072.6	Q15573-1
	TAF1A	ENST00000972077.1		c.280G>C	p.Ala94Pro	missense	Exon 3 of 12	ENSP00000642136.1
	TAF1A	ENST00000350027.8	TSL:2	c.280G>C	p.Ala94Pro	missense	Exon 3 of 12	ENSP00000339976.4	Q15573-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	6.7
DANN	Benign	0.92
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.035
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.15
Sift	Benign	0.26	T
Sift4G	Benign	0.28	T
Polyphen		0.85	P
Vest4		0.24
MutPred		0.37		Gain of loop (P = 0.0166)
MVP		0.41
MPC		0.67
ClinPred		0.28	T
GERP RS		2.9
Varity_R		0.12
gMVP		0.46
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs956228152; hg19: chr1-222757481;