Variant 2-48962839-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000145.4(FSHR):c.1982C>T(p.Thr661Ile) 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 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FSHR
NM_000145.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

FSHR (HGNC:3969): (follicle stimulating hormone receptor) The protein encoded by this gene belongs to family 1 of G-protein coupled receptors. It is the receptor for follicle stimulating hormone and functions in gonad development. Mutations in this gene cause ovarian dysgenesis type 1, and also ovarian hyperstimulation syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

FSHR links:

ENSG00000282890 (HGNC:):

ENSG00000282890 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11616945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSHR	NM_000145.4 linkuse as main transcript	c.1982C>T	p.Thr661Ile	missense_variant	10/10	ENST00000406846.7	NP_000136.2	P23945A0A1D5RMN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FSHR	ENST00000406846.7 linkuse as main transcript	c.1982C>T	p.Thr661Ile	missense_variant	10/10	1	NM_000145.4	ENSP00000384708.2	A0A1D5RMN4
FSHR	ENST00000304421.8 linkuse as main transcript	c.1904C>T	p.Thr635Ile	missense_variant	9/9	1		ENSP00000306780.4	P23945
ENSG00000282890	ENST00000634588.1 linkuse as main transcript	n.492+16434G>A		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727230

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.1982C>T (p.T661I) alteration is located in exon 10 (coding exon 10) of the FSHR gene. This alteration results from a C to T substitution at nucleotide position 1982, causing the threonine (T) at amino acid position 661 to be replaced by an isoleucine (I). 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

Benign

0.092

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.93

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.61

T;.

M_CAP

Benign

0.023

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.88

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.85

N;N

REVEL

Benign

0.15

Sift

Benign

0.090

T;T

Sift4G

Benign

0.20

T;T

Vest4

0.046

MutPred

0.20

Loss of glycosylation at T661 (P = 0.0063);.;

MVP

0.85

MPC

0.025

ClinPred

0.065

GERP RS

-0.85

gMVP

0.46

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over