11-30233594-A-T

Position:

• chr11-30233594-A-T

Variant summary

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

The NM_001382289.1(FSHB):​c.184A>T​(p.Arg62Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FSHB NM_001382289.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15

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:):

ACMG classification

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/exons	MANE	Protein	UniProt
FSHB	NM_001382289.1	c.184A>T	p.Arg62Trp	missense_variant	3/3	ENST00000533718.2	NP_001369218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSHB	ENST00000533718.2	c.184A>T	p.Arg62Trp	missense_variant	3/3	1	NM_001382289.1	ENSP00000433424.1
FSHB	ENST00000254122.8	c.184A>T	p.Arg62Trp	missense_variant	3/3	5		ENSP00000254122.3
FSHB	ENST00000417547.1	c.184A>T	p.Arg62Trp	missense_variant	3/3	5		ENSP00000416606.1
ARL14EP-DT	ENST00000662729.1	n.293-76741T>A		intron_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 31, 2021

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with FSHB-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 62 of the FSHB protein (p.Arg62Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D;D;D
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.92	.;.;D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Uncertain	0.082	D
MutationAssessor	Uncertain	2.4	M;M;M
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.53
Sift	Benign	0.052	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.95	P;P;P
Vest4		0.32
MutPred		0.41		Loss of disorder (P = 0.0346);Loss of disorder (P = 0.0346);Loss of disorder (P = 0.0346);
MVP		0.93
MPC		0.48
ClinPred		0.96	D
GERP RS		-0.88
Varity_R		0.50
gMVP		0.58

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: chr11-30255141;