chr11-30231961-G-A

Variant names:

• chr11-30231961-G-A
• NM_001382289.1:c.59G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001382289.1(FSHB):​c.59G>A​(p.Ser20Asn) 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 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FSHB NM_001382289.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.828

Genes affected

FSHB (HGNC:3964): (follicle stimulating hormone subunit beta) The pituitary glycoprotein hormone family includes follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, and thyroid-stimulating hormone. All of these glycoproteins consist of an identical alpha subunit and a hormone-specific beta subunit. This gene encodes the beta subunit of follicle-stimulating hormone. In conjunction with luteinizing hormone, follicle-stimulating hormone induces egg and sperm production. Alternative splicing results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ARL14EP-DT (HGNC:55517): (ARL14EP divergent transcript)

ACMG classification

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=0.36843023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHB	NM_001382289.1	c.59G>A	p.Ser20Asn	missense_variant	Exon 2 of 3	ENST00000533718.2	NP_001369218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHB	ENST00000533718.2	c.59G>A	p.Ser20Asn	missense_variant	Exon 2 of 3	1	NM_001382289.1	ENSP00000433424.1
FSHB	ENST00000254122.8	c.59G>A	p.Ser20Asn	missense_variant	Exon 2 of 3	5		ENSP00000254122.3
FSHB	ENST00000417547.1	c.59G>A	p.Ser20Asn	missense_variant	Exon 2 of 3	5		ENSP00000416606.1
ARL14EP-DT	ENST00000662729.1	n.293-75108C>T		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461654 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727130

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.72	D;D;D
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.020
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.70	.;.;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.64	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.42	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.26
MutPred		0.41		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.96
MPC		0.21
ClinPred		0.14	T
GERP RS		4.9
Varity_R		0.26
gMVP		0.61

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: chr11-30253508;