dbSNP rs1390964419: INHBA:p.Gly277Cys (chr7-41690102-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002192.4(INHBA):c.829G>T(p.Gly277Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G277S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

INHBA
NM_002192.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.186

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2672627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHBA	NM_002192.4 link	c.829G>T	p.Gly277Cys	missense_variant	Exon 3 of 3	ENST00000242208.5	NP_002183.1	P08476A4D1W7
INHBA	XM_017012174.2 link	c.829G>T	p.Gly277Cys	missense_variant	Exon 3 of 3		XP_016867663.2	P08476A4D1W7
INHBA	XM_047420335.1 link	c.829G>T	p.Gly277Cys	missense_variant	Exon 4 of 4		XP_047276291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHBA	ENST00000242208.5 link	c.829G>T	p.Gly277Cys	missense_variant	Exon 3 of 3	1	NM_002192.4	ENSP00000242208.4		P08476

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461646

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.0046

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

D;D;D

Eigen

Benign

-0.096

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.50

.;.;T

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.1

L;L;L

PrimateAI

Benign

0.46

PROVEAN

Benign

0.040

N;N;.

REVEL

Benign

0.28

Sift

Uncertain

0.012

D;D;.

Sift4G

Uncertain

0.0070

D;D;.

Polyphen

0.91

P;P;P

Vest4

0.23

MutPred

0.29

Gain of ubiquitination at K272 (P = 0.1375);Gain of ubiquitination at K272 (P = 0.1375);Gain of ubiquitination at K272 (P = 0.1375);

MVP

0.68

MPC

1.1

ClinPred

0.37

GERP RS

5.6

Varity_R

0.13

gMVP

0.79

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over