7-41700181-A-G

Position:

• chr7-41700181-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002192.4(INHBA):​c.194T>C​(p.Met65Thr) 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: 29)
• Consequence: INHBA NM_002192.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.10

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]

INHBA-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INHBA	NM_002192.4	c.194T>C	p.Met65Thr	missense_variant	2/3	ENST00000242208.5	NP_002183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INHBA	ENST00000242208.5	c.194T>C	p.Met65Thr	missense_variant	2/3	1	NM_002192.4	ENSP00000242208.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.194T>C (p.M65T) alteration is located in exon 2 (coding exon 1) of the INHBA gene. This alteration results from a T to C substitution at nucleotide position 194, causing the methionine (M) at amino acid position 65 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D;D;D
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	.;.;T
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.3	M;M;M
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.7	N;N;.
REVEL	Uncertain	0.46
Sift	Benign	0.12	T;T;.
Sift4G	Benign	0.12	T;T;.
Polyphen		1.0	D;D;D
Vest4		0.76
MutPred		0.62		Loss of MoRF binding (P = 0.075);Loss of MoRF binding (P = 0.075);Loss of MoRF binding (P = 0.075);
MVP		0.73
MPC		1.6
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.53
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-41739779;