chr1-222561466-G-C

Variant names:

• chr1-222561466-G-C
• rs1659912774
• NM_005681.4:c.1138C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005681.4(TAF1A):​c.1138C>G​(p.Pro380Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.82
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.791

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.1138C>G	p.Pro380Ala	missense	Exon 10 of 11	NP_005672.1	Q15573-1
	TAF1A	NM_001201536.1		c.1138C>G	p.Pro380Ala	missense	Exon 10 of 12	NP_001188465.1	A8K4K5
	TAF1A	NM_139352.2		c.796C>G	p.Pro266Ala	missense	Exon 9 of 11	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.1138C>G	p.Pro380Ala	missense	Exon 10 of 11	ENSP00000327072.6	Q15573-1
	TAF1A	ENST00000972077.1		c.1273C>G	p.Pro425Ala	missense	Exon 11 of 12	ENSP00000642136.1
	TAF1A	ENST00000350027.8	TSL:2	c.1138C>G	p.Pro380Ala	missense	Exon 10 of 12	ENSP00000339976.4	Q15573-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.8
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.38
Sift	Benign	0.078	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.51		Gain of helix (P = 0.0078)
MVP		0.89
MPC		0.89
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.17
gMVP		0.37
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1659912774; hg19: chr1-222734808;