1-204190409-T-TGCCC
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2
The NM_002256.4(KISS1):c.*74_*75insGGGC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000082 ( 0 hom., cov: 18)
Exomes 𝑓: 0.00059 ( 3 hom. )
Consequence
KISS1
NM_002256.4 3_prime_UTR
NM_002256.4 3_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.335
Publications
0 publications found
Genes affected
KISS1 (HGNC:6341): (KiSS-1 metastasis suppressor) This gene is a metastasis suppressor gene that suppresses metastases of melanomas and breast carcinomas without affecting tumorigenicity. The encoded protein may inhibit chemotaxis and invasion and thereby attenuate metastasis in malignant melanomas. Studies suggest a putative role in the regulation of events downstream of cell-matrix adhesion, perhaps involving cytoskeletal reorganization. A protein product of this gene, kisspeptin, stimulates gonadotropin-releasing hormone (GnRH)-induced gonadotropin secretion and regulates the pubertal activation of GnRH neurons. A polymorphism in the terminal exon of this mRNA results in two protein isoforms. An adenosine present at the polymorphic site represents the third position in a stop codon. When the adenosine is absent, a downstream stop codon is utilized and the encoded protein extends for an additional seven amino acid residues. [provided by RefSeq, Jun 2022]
REN (HGNC:9958): (renin) This gene encodes renin, an aspartic protease that is secreted by the kidneys. Renin is a part of the renin-angiotensin-aldosterone system involved in regulation of blood pressure, and electrolyte balance. This enzyme catalyzes the first step in the activation pathway of angiotensinogen by cleaving angiotensinogen to form angiotensin I, which is then converted to angiotensin II by angiotensin I converting enzyme. This cascade can result in aldosterone release, narrowing of blood vessels, and increase in blood pressure as angiotension II is a vasoconstrictive peptide. Transcript variants that encode different protein isoforms and that arise from alternative splicing and the use of alternative promoters have been described, but their full-length nature has not been determined. Mutations in this gene have been shown to cause hyperuricemic nephropathy familial juvenile 2, familial hyperproreninemia, and renal tubular dysgenesis. [provided by RefSeq, May 2020]
REN Gene-Disease associations (from GenCC):
- familial juvenile hyperuricemic nephropathy type 2Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
- renal tubular dysgenesis of genetic originInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
BS2
High Homozygotes in GnomAdExome4 at 3 AR,AD gene
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_002256.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| KISS1 | NM_002256.4 | MANE Select | c.*74_*75insGGGC | 3_prime_UTR | Exon 3 of 3 | NP_002247.3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KISS1 | ENST00000367194.5 | TSL:1 MANE Select | c.*74_*75insGGGC | 3_prime_UTR | Exon 3 of 3 | ENSP00000356162.4 | Q15726 | ||
| KISS1 | ENST00000882445.1 | c.*74_*75insGGGC | 3_prime_UTR | Exon 2 of 2 | ENSP00000552504.1 | ||||
| REN | ENST00000638118.1 | TSL:5 | c.-389_-388insGGGC | upstream_gene | N/A | ENSP00000490307.1 | A0A1B0GUZ2 |
Frequencies
GnomAD3 genomes 0.00000823 AC: 1AN: 121440Hom.: 0 Cov.: 18 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
121440
Hom.:
Cov.:
18
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: 0.000590 AC: 266AN: 450498Hom.: 3 Cov.: 0 AF XY: 0.000564 AC XY: 138AN XY: 244896 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
266
AN:
450498
Hom.:
Cov.:
0
AF XY:
AC XY:
138
AN XY:
244896
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
16
AN:
10858
American (AMR)
AF:
AC:
9
AN:
28364
Ashkenazi Jewish (ASJ)
AF:
AC:
4
AN:
15740
East Asian (EAS)
AF:
AC:
24
AN:
23160
South Asian (SAS)
AF:
AC:
2
AN:
58640
European-Finnish (FIN)
AF:
AC:
8
AN:
24482
Middle Eastern (MID)
AF:
AC:
2
AN:
1822
European-Non Finnish (NFE)
AF:
AC:
183
AN:
263642
Other (OTH)
AF:
AC:
18
AN:
23790
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.315
Heterozygous variant carriers
0
26
52
77
103
129
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00000823 AC: 1AN: 121498Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0AN XY: 58910 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
121498
Hom.:
Cov.:
18
AF XY:
AC XY:
0
AN XY:
58910
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
30222
American (AMR)
AF:
AC:
0
AN:
12410
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2924
East Asian (EAS)
AF:
AC:
0
AN:
3608
South Asian (SAS)
AF:
AC:
0
AN:
3964
European-Finnish (FIN)
AF:
AC:
0
AN:
8100
Middle Eastern (MID)
AF:
AC:
0
AN:
248
European-Non Finnish (NFE)
AF:
AC:
0
AN:
57592
Other (OTH)
AF:
AC:
0
AN:
1674
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.