rs1187807999
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_005543.4(INSL3):c.148del(p.Arg50AlafsTer77) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,548,578 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 35)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
INSL3
NM_005543.4 frameshift
NM_005543.4 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.266
Genes affected
INSL3 (HGNC:6086): (insulin like 3) This gene encodes a member of the insulin-like hormone superfamily. The encoded protein is mainly produced in gonadal tissues. Studies of the mouse counterpart suggest that this gene may be involved in the development of urogenital tract and female fertility. This protein may also act as a hormone to regulate growth and differentiation of gubernaculum, and thus mediating intra-abdominal testicular descent. Mutations in this gene may lead to cryptorchidism. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
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 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.626 CDS is truncated, and there are 1 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 |
|---|---|---|---|---|---|---|---|---|
| INSL3 | NM_005543.4 | c.148del | p.Arg50AlafsTer77 | frameshift_variant | 1/2 | ENST00000317306.8 | NP_005534.2 | |
| INSL3 | NM_001265587.2 | c.148del | p.Arg50AlafsTer29 | frameshift_variant | 1/3 | NP_001252516.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| INSL3 | ENST00000317306.8 | c.148del | p.Arg50AlafsTer77 | frameshift_variant | 1/2 | 1 | NM_005543.4 | ENSP00000321724 | P1 | |
| INSL3 | ENST00000379695.5 | c.148del | p.Arg50AlafsTer29 | frameshift_variant | 1/3 | 1 | ENSP00000369017 | |||
| INSL3 | ENST00000598577.1 | c.147del | p.Arg50AlafsTer90 | frameshift_variant | 1/2 | 1 | ENSP00000469309 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 35
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GnomAD4 exome AF: 0.00000215 AC: 3AN: 1396344Hom.: 0 Cov.: 63 AF XY: 0.00000145 AC XY: 1AN XY: 688786
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GnomAD4 genome 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 35 AF XY: 0.0000134 AC XY: 1AN XY: 74372
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at