7-41689881-G-C

Position:

• chr7-41689881-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002192.4(INHBA):​c.1050C>G​(p.Cys350Trp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: INHBA NM_002192.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.159

Genes affected

INHBA (HGNC:6066): (inhibin subunit beta A) 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 the dimeric activin and inhibin protein complexes. These complexes activate and inhibit, respectively, follicle stimulating hormone secretion from the pituitary gland. The encoded protein also plays a role in eye, tooth and testis development. Elevated expression of this gene may be associated with cancer cachexia in human patients. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.995

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INHBA	NM_002192.4	c.1050C>G	p.Cys350Trp	missense_variant	3/3	ENST00000242208.5	NP_002183.1
INHBA	XM_017012174.2	c.1050C>G	p.Cys350Trp	missense_variant	3/3		XP_016867663.2
INHBA	XM_047420335.1	c.1050C>G	p.Cys350Trp	missense_variant	4/4		XP_047276291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INHBA	ENST00000242208.5	c.1050C>G	p.Cys350Trp	missense_variant	3/3	1	NM_002192.4	ENSP00000242208.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

-

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.98	D;D;D
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	1.0	.;.;D
M_CAP	Pathogenic	0.84	D
MetaRNN	Pathogenic	1.0	D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.4	H;H;H
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-10	D;D;.
REVEL	Pathogenic	0.92
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;.
Polyphen		1.0	D;D;D
Vest4		0.85
MutPred		0.97		Gain of catalytic residue at C350 (P = 0.1043);Gain of catalytic residue at C350 (P = 0.1043);Gain of catalytic residue at C350 (P = 0.1043);
MVP		1.0
MPC		2.1
ClinPred		1.0	D
GERP RS		-0.63
Varity_R		0.98
gMVP		1.0

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: rs1562565534; hg19: chr7-41729479;