rs149435555

Variant names:

• chr2-157541093-C-A
• rs149435555
• NM_145259.3:c.1222G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-157541093-C-A
• chr2-157541093-C-T

Variant summary

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

The NM_145259.3(ACVR1C):​c.1222G>T​(p.Gly408*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACVR1C NM_145259.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

Genes affected

ACVR1C (HGNC:18123): (activin A receptor type 1C) ACVR1C is a type I receptor for the TGFB (see MIM 190180) family of signaling molecules. Upon ligand binding, type I receptors phosphorylate cytoplasmic SMAD transcription factors, which then translocate to the nucleus and interact directly with DNA or in complex with other transcription factors (Bondestam et al., 2001 [PubMed 12063393]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.1222G>T	p.Gly408*	stop_gained	Exon 7 of 9	ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.1072G>T	p.Gly358*	stop_gained	Exon 7 of 9		NP_001104501.1
ACVR1C	NM_001111032.2	c.982G>T	p.Gly328*	stop_gained	Exon 6 of 8		NP_001104502.1
ACVR1C	NM_001111033.2	c.751G>T	p.Gly251*	stop_gained	Exon 5 of 7		NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.1222G>T	p.Gly408*	stop_gained	Exon 7 of 9	1	NM_145259.3	ENSP00000243349.7
ACVR1C	ENST00000409680.7	c.1072G>T	p.Gly358*	stop_gained	Exon 7 of 9	1		ENSP00000387168.3
ACVR1C	ENST00000335450.7	c.982G>T	p.Gly328*	stop_gained	Exon 6 of 8	1		ENSP00000335178.7
ACVR1C	ENST00000348328.9	c.751G>T	p.Gly251*	stop_gained	Exon 5 of 7	1		ENSP00000335139.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248680 Hom.: 0 AF XY: 0.00000744 AC XY: 1 AN XY: 134408

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.91	D
Vest4		0.94
GERP RS		3.5

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

LitVar

Other links and lift over

dbSNP: rs149435555; hg19: chr2-158397605;