rs1187807999
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_005543.4(INSL3):c.148delC(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
Publications
2 publications found
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]
INSL3 Gene-Disease associations (from GenCC):
- cryptorchidismInheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
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 7 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| INSL3 | ENST00000317306.8 | c.148delC | p.Arg50AlafsTer77 | frameshift_variant | Exon 1 of 2 | 1 | NM_005543.4 | ENSP00000321724.6 | ||
| INSL3 | ENST00000379695.5 | c.148delC | p.Arg50AlafsTer29 | frameshift_variant | Exon 1 of 3 | 1 | ENSP00000369017.4 | |||
| INSL3 | ENST00000598577.1 | c.145delC | p.Arg49fs | frameshift_variant | Exon 1 of 2 | 1 | ENSP00000469309.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 35 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152234
Hom.:
Cov.:
35
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000705 AC: 1AN: 141890 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
141890
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000215 AC: 3AN: 1396344Hom.: 0 Cov.: 63 AF XY: 0.00000145 AC XY: 1AN XY: 688786 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
3
AN:
1396344
Hom.:
Cov.:
63
AF XY:
AC XY:
1
AN XY:
688786
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
31564
American (AMR)
AF:
AC:
0
AN:
35698
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25132
East Asian (EAS)
AF:
AC:
0
AN:
35718
South Asian (SAS)
AF:
AC:
0
AN:
79186
European-Finnish (FIN)
AF:
AC:
1
AN:
46998
Middle Eastern (MID)
AF:
AC:
0
AN:
5560
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1078562
Other (OTH)
AF:
AC:
1
AN:
57926
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000178044), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 35 AF XY: 0.0000134 AC XY: 1AN XY: 74372 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152234
Hom.:
Cov.:
35
AF XY:
AC XY:
1
AN XY:
74372
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41468
American (AMR)
AF:
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5186
South Asian (SAS)
AF:
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
AC:
1
AN:
10626
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68038
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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