rs374067342

Variant names:

• chr12-57449922-C-A
• rs374067342
• NM_005538.4:c.959C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-57449922-C-A
• chr12-57449922-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005538.4(INHBC):​c.959C>A​(p.Thr320Lys) variant causes a missense change. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INHBC NM_005538.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.97

Genes affected

INHBC (HGNC:6068): (inhibin subunit beta C) This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate a subunit of homodimeric and heterodimeric activin complexes. The heterodimeric complex may function in the inhibition of activin A signaling. Transgenic mice overexpressing this gene exhibit defects in testis, liver and prostate. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.916

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHBC	NM_005538.4	c.959C>A	p.Thr320Lys	missense_variant	Exon 2 of 2	ENST00000309668.3	NP_005529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHBC	ENST00000309668.3	c.959C>A	p.Thr320Lys	missense_variant	Exon 2 of 2	1	NM_005538.4	ENSP00000308716.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.88	D
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.68		Gain of catalytic residue at T320 (P = 0);
MVP		0.98
MPC		0.78
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.82
gMVP		0.92

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: rs374067342; hg19: chr12-57843705; COSMIC: COSV59004590; COSMIC: COSV59004590;