2-48962782-C-G

Variant names:

Variant summary

Our verdict is The variant received 1 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_ModerateB3_Supporting

The NM_000145.4(FSHR):c.2039G>C (p.Ser680Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The gene FSHR is a known oncogene (CancerMine: 1 oncogene citations). The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.S680N: Benign (ClinVar VariationId 16247, 2 stars)

Frequency

Genomes: not found (cov: 32)

Consequence

FSHR
NM_000145.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0530

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

ovarian hyperstimulation syndrome
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
ovarian dysgenesis 1
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
46 XX gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FSHR links:

MIR548BAHG (HGNC:58158):

MIR548BAHG links:

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new If you want to explore the variant's impact on the transcript NM_000145.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 points.

Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Computational evidence does not support a deleterious effect; Missense variant — primary computational scorer does not support an oncogenic/deleterious effect; supports B3

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000145.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	NM_000145.4	MANE Select	c.2039G>C	p.Ser680Thr	missense	Exon 10 of 10	NP_000136.2
	FSHR	NM_181446.3		c.1961G>C	p.Ser654Thr	missense	Exon 9 of 9	NP_852111.2	P23945-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FSHR	ENST00000406846.7	TSL:1 MANE Select	c.2039G>C	p.Ser680Thr	missense	Exon 10 of 10	ENSP00000384708.2	P23945-1
FSHR	ENST00000304421.8	TSL:1	c.1961G>C	p.Ser654Thr	missense	Exon 9 of 9	ENSP00000306780.4	P23945-3
MIR548BAHG	ENST00000634588.1	TSL:5	n.492+16377C>G		intron	N/A

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes					32
GnomAD4 exome					48
GnomAD4 genome					32

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Benign	-	1.1
AlphaMissense	Benign	-	0.064
BayesDel_addAF	Benign	T	-0.19
BayesDel_noAF	Benign	-	-0.52
CADD	Benign	-	0.59
DANN	Benign	-	0.79
Eigen	Benign	-	-0.84
Eigen_PC	Benign	-	-0.83
FATHMM_MKL	Benign	N	0.39
FuncVEP CTI	Benign	-	0.084
GPN-Star LLR	N/A	-	-1.4
GPN-Star score	N/A	-	1.4
LIST_S2	Benign	T	0.26
M_CAP	Benign	D	0.049
MetaRNN	Benign	T	0.099
MetaSVM	Benign	T	-0.90
Mutation Taster	N/A	polymorphism	97/3
PhyloP100	Benign	-	0.053
popEVE	Benign	-	-2.5
PrimateAI	Benign	T	0.25
PROVEAN	Benign	N	-0.83
REVEL	Benign	-	0.040
Sift	Benign	T	0.17
Sift4G	Benign	T	0.60
VESM-3B	Benign	-	-3.4

Showing 25 of 25 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.0
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.0

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

Publications

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