NM_032551.5:c.991C>T
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_032551.5(KISS1R):c.991C>T(p.Arg331*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,589,806 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 Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
KISS1R
NM_032551.5 stop_gained
NM_032551.5 stop_gained
Scores
2
4
Clinical Significance
Conservation
PhyloP100: 0.123
Publications
14 publications found
Genes affected
KISS1R (HGNC:4510): (KISS1 receptor) The protein encoded by this gene is a galanin-like G protein-coupled receptor that binds metastin, a peptide encoded by the metastasis suppressor gene KISS1. The tissue distribution of the expressed gene suggests that it is involved in the regulation of endocrine function, and this is supported by the finding that this gene appears to play a role in the onset of puberty. Mutations in this gene have been associated with hypogonadotropic hypogonadism and central precocious puberty. [provided by RefSeq, Jul 2008]
KISS1R Gene-Disease associations (from GenCC):
- hypogonadotropic hypogonadism 8 with or without anosmiaInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- hypogonadotropic hypogonadismInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- central precocious puberty 1Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.172 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-920542-C-T is Pathogenic according to our data. Variant chr19-920542-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 5756.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_032551.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KISS1R | NM_032551.5 | MANE Select | c.991C>T | p.Arg331* | stop_gained | Exon 5 of 5 | NP_115940.2 | Q969F8 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KISS1R | ENST00000234371.10 | TSL:1 MANE Select | c.991C>T | p.Arg331* | stop_gained | Exon 5 of 5 | ENSP00000234371.3 | Q969F8 | |
| KISS1R | ENST00000909146.1 | c.985C>T | p.Arg329* | stop_gained | Exon 5 of 5 | ENSP00000579205.1 | |||
| KISS1R | ENST00000606939.2 | TSL:5 | c.*77C>T | 3_prime_UTR | Exon 4 of 4 | ENSP00000475639.1 | U3KQ86 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152118Hom.: 0 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152118
Hom.:
Cov.:
34
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:
GnomAD4 exome AF: 6.96e-7 AC: 1AN: 1437688Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0AN XY: 715474 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1437688
Hom.:
Cov.:
37
AF XY:
AC XY:
0
AN XY:
715474
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30300
American (AMR)
AF:
AC:
0
AN:
42672
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25418
East Asian (EAS)
AF:
AC:
0
AN:
36898
South Asian (SAS)
AF:
AC:
0
AN:
83390
European-Finnish (FIN)
AF:
AC:
0
AN:
50244
Middle Eastern (MID)
AF:
AC:
0
AN:
5658
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1103642
Other (OTH)
AF:
AC:
0
AN:
59466
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152118Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74312 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152118
Hom.:
Cov.:
34
AF XY:
AC XY:
1
AN XY:
74312
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41438
American (AMR)
AF:
AC:
0
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5200
South Asian (SAS)
AF:
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
AC:
0
AN:
10590
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67992
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
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.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Hypogonadotropic hypogonadism 8 without anosmia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
PhyloP100
Vest4
GERP RS
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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