chr19-49016208-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000894.3(LHB):c.286G>A(p.Val96Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000949 in 1,612,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000894.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LHB | NM_000894.3 | c.286G>A | p.Val96Met | missense_variant | Exon 3 of 3 | ENST00000649238.3 | NP_000885.1 | |
LHB | XM_047438832.1 | c.334G>A | p.Val112Met | missense_variant | Exon 2 of 2 | XP_047294788.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000558 AC: 14AN: 251104Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135826
GnomAD4 exome AF: 0.0000890 AC: 130AN: 1460292Hom.: 0 Cov.: 87 AF XY: 0.0000812 AC XY: 59AN XY: 726488
GnomAD4 genome AF: 0.000151 AC: 23AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74348
ClinVar
Submissions by phenotype
not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32763379) -
Isolated lutropin deficiency Uncertain:1
variant was observed with the other variant in TACR3 gene (NM_001059.2:c.737+1G>A, MIM:614840 ), maternal origin, both observed in heterozygote status and in digenic pattern of inheritance for idiopatic hypogonadotropic hypogonadism/Kallmann syndrome -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at