11-30231908-G-T

Variant names:

• chr11-30231908-G-T
• NM_001382289.1:c.6G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001382289.1(FSHB):​c.6G>T​(p.Lys2Asn) 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 1,461,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 3.19

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHB	NM_001382289.1	c.6G>T	p.Lys2Asn	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.6G>T	p.Lys2Asn	missense_variant	Exon 2 of 3	1	NM_001382289.1	ENSP00000433424.1
FSHB	ENST00000254122.8	c.6G>T	p.Lys2Asn	missense_variant	Exon 2 of 3	5		ENSP00000254122.3
FSHB	ENST00000417547.1	c.6G>T	p.Lys2Asn	missense_variant	Exon 2 of 3	5		ENSP00000416606.1
ARL14EP-DT	ENST00000662729.1	n.293-75055C>A		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461510 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727054

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	0.22
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D;D;D
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.28	.;.;T
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.97	N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.015	D;D;D
Sift4G	Benign	0.10	T;T;T
Polyphen		0.92	P;P;P
Vest4		0.50
MutPred		0.33		Loss of ubiquitination at K2 (P = 0.0174);Loss of ubiquitination at K2 (P = 0.0174);Loss of ubiquitination at K2 (P = 0.0174);
MVP		0.89
MPC		0.62
ClinPred		0.84	D
GERP RS		3.9
Varity_R		0.12
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: chr11-30253455;