rs6165

Variant names:

• chr2-48963902-C-A
• rs6165
• NM_000145.4:c.919G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-48963902-C-A
• chr2-48963902-C-G
• chr2-48963902-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_000145.4(FSHR):​c.919G>T​(p.Ala307Ser) 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 benign outcome for this variant. 16/20 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. A307T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FSHR NM_000145.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 229 publications found

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 Gene-Disease associations (from GenCC):

• ovarian hyperstimulation syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• ovarian dysgenesis 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000282890 (HGNC:58158):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 23 curated pathogenic missense variants (we use a threshold of 10). The gene has 4 curated benign missense variants. Gene score misZ: -0.79874 (below the threshold of 3.09). Trascript score misZ: -0.97417 (below the threshold of 3.09). GenCC associations: The gene is linked to ovarian hyperstimulation syndrome, ovarian dysgenesis 1, 46 XX gonadal dysgenesis.
• BP4: Computational evidence support a benign effect (MetaRNN=0.087227374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.919G>T	p.Ala307Ser	missense_variant	Exon 10 of 10	ENST00000406846.7	NP_000136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.919G>T	p.Ala307Ser	missense_variant	Exon 10 of 10	1	NM_000145.4	ENSP00000384708.2
FSHR	ENST00000304421.8	c.841G>T	p.Ala281Ser	missense_variant	Exon 9 of 9	1		ENSP00000306780.4
FSHR	ENST00000454032.5	c.733G>T	p.Ala245Ser	missense_variant	Exon 9 of 9	1		ENSP00000415504.1
ENSG00000282890	ENST00000634588.1	n.492+17497C>A		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.1
DANN	Benign	0.57
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.71	T;.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.087	T;T;T
MetaSVM	Benign	-0.96	T
PhyloP100		0.022
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.44	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.95	T;T;T
Sift4G	Benign	0.83	T;T;.
Vest4		0.18
MutPred		0.34		Gain of disorder (P = 0.0234);.;.;
MVP		0.82
MPC		0.023
ClinPred		0.98	D
GERP RS		1.8
gMVP		0.56
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs6165; hg19: chr2-49191041;