11-30232049-C-G

Variant names:

• chr11-30232049-C-G
• rs1157096893
• NM_001382289.1:c.147C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001382289.1(FSHB):​c.147C>G​(p.Tyr49*) 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. Y49Y) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FSHB NM_001382289.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382289.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHB	NM_001382289.1	MANE Select	c.147C>G	p.Tyr49*	stop_gained	Exon 2 of 3	NP_001369218.1	A0A0F7RQE8
	FSHB	NM_000510.4		c.147C>G	p.Tyr49*	stop_gained	Exon 2 of 3	NP_000501.1	P01225
	FSHB	NM_001018080.3		c.147C>G	p.Tyr49*	stop_gained	Exon 2 of 3	NP_001018090.1	A0A0F7RQE8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHB	ENST00000533718.2	TSL:1 MANE Select	c.147C>G	p.Tyr49*	stop_gained	Exon 2 of 3	ENSP00000433424.1	P01225
	FSHB	ENST00000254122.8	TSL:5	c.147C>G	p.Tyr49*	stop_gained	Exon 2 of 3	ENSP00000254122.3	P01225
	FSHB	ENST00000417547.1	TSL:5	c.147C>G	p.Tyr49*	stop_gained	Exon 2 of 3	ENSP00000416606.1	P01225

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.81	D
PhyloP100		0.23
Vest4		0.95
GERP RS		1.8
Mutation Taster		=28/172	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1157096893; hg19: chr11-30253596;