Variant rs926067580 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001382289.1(FSHB):c.162T>A(p.Asp54Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

FSHB
NM_001382289.1 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.162

Variant links:

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]

FSHB links:

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

ARL14EP-DT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHB	NM_001382289.1 link	c.162T>A	p.Asp54Glu	missense_variant, splice_region_variant	Exon 3 of 3	ENST00000533718.2	NP_001369218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FSHB	ENST00000533718.2 link	c.162T>A	p.Asp54Glu	missense_variant, splice_region_variant	Exon 3 of 3	1	NM_001382289.1	ENSP00000433424.1	P01225
FSHB	ENST00000254122.8 link	c.162T>A	p.Asp54Glu	missense_variant, splice_region_variant	Exon 3 of 3	5		ENSP00000254122.3	P01225
FSHB	ENST00000417547.1 link	c.162T>A	p.Asp54Glu	missense_variant, splice_region_variant	Exon 3 of 3	5		ENSP00000416606.1	P01225
ARL14EP-DT	ENST00000662729.1 link	n.293-76719A>T		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.80

D;D;D

Eigen

Benign

-0.047

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.75

.;.;T

M_CAP

Uncertain

0.096

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Uncertain

0.032

MutationAssessor

Benign

2.0

M;M;M

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.3

N;N;N

REVEL

Uncertain

0.59

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.98

D;D;D

Vest4

0.56

MutPred

0.65

Gain of methylation at K58 (P = 0.1393);Gain of methylation at K58 (P = 0.1393);Gain of methylation at K58 (P = 0.1393);

MVP

0.93

MPC

0.63

ClinPred

0.88

GERP RS

-1.8

Varity_R

0.29

gMVP

0.75

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over