11-30233638-C-A

Position:

• chr11-30233638-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The ENST00000533718.2(FSHB):​c.228C>A​(p.Tyr76Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y76Y) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FSHB ENST00000533718.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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 Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSHB	NM_001382289.1	c.228C>A	p.Tyr76Ter	stop_gained	3/3	ENST00000533718.2	NP_001369218.1
ARL14EP-DT	XR_007062639.1	n.351+83252G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSHB	ENST00000533718.2	c.228C>A	p.Tyr76Ter	stop_gained	3/3	1	NM_001382289.1	ENSP00000433424	P1
ARL14EP-DT	ENST00000662729.1	n.293-76785G>T		intron_variant, non_coding_transcript_variant
FSHB	ENST00000254122.8	c.228C>A	p.Tyr76Ter	stop_gained	3/3	5		ENSP00000254122	P1
FSHB	ENST00000417547.1	c.228C>A	p.Tyr76Ter	stop_gained	3/3	5		ENSP00000416606	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	20
DANN	Benign	0.97
Eigen	Benign	-0.77
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.074	N
MutationTaster	Benign	5.3e-18	P;P;P
Vest4		0.84
GERP RS		-8.5

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: chr11-30255185;