rs10407968

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032551.5(KISS1R):c.24A>G(p.Gly8Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,503,474 control chromosomes in the GnomAD database, including 17,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2605 hom., cov: 33)

Exomes 𝑓: 0.15 ( 15241 hom. )

Consequence

KISS1R
NM_032551.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.89

Publications

18 publications found

Variant links:

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 anosmia
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
hypogonadotropic hypogonadism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
central precocious puberty 1
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

KISS1R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-917526-A-G is Benign according to our data. Variant chr19-917526-A-G is described in ClinVar as Benign. ClinVar VariationId is 286524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KISS1R	NM_032551.5 link	c.24A>G	p.Gly8Gly	synonymous_variant	Exon 1 of 5	ENST00000234371.10	NP_115940.2	Q969F8
KISS1R	XM_047439545.1 link	c.24A>G	p.Gly8Gly	synonymous_variant	Exon 1 of 4		XP_047295501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KISS1R	ENST00000234371.10 link	c.24A>G	p.Gly8Gly	synonymous_variant	Exon 1 of 5	1	NM_032551.5	ENSP00000234371.3	Q969F8
KISS1R	ENST00000606939.2 link	c.24A>G	p.Gly8Gly	synonymous_variant	Exon 1 of 4	5		ENSP00000475639.1	U3KQ86
KISS1R	ENST00000592648.1 link	c.24A>G	p.Gly8Gly	synonymous_variant	Exon 1 of 2	5		ENSP00000467666.1	K7EQ45

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27245

AN:

151980

Hom.:

2595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.175

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.182

GnomAD2 exomes

AF:

0.157

AC:

16996

AN:

108192

AF XY:

0.158

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.147

AC:

198230

AN:

1351384

Hom.:

15241

Cov.:

AF XY:

0.149

AC XY:

99287

AN XY:

664556

show subpopulations

African (AFR)

AF:

0.226

AC:

6431

AN:

28398

American (AMR)

AF:

0.186

AC:

5925

AN:

31922

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

4453

AN:

23174

East Asian (EAS)

AF:

0.151

AC:

5053

AN:

33552

South Asian (SAS)

AF:

0.223

AC:

16619

AN:

74514

European-Finnish (FIN)

AF:

0.163

AC:

5685

AN:

34868

Middle Eastern (MID)

AF:

0.201

AC:

962

AN:

4780

European-Non Finnish (NFE)

AF:

0.135

AC:

144069

AN:

1063864

Other (OTH)

AF:

0.160

AC:

9033

AN:

56312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

9259

18519

27778

37038

46297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5370

10740

16110

21480

26850

<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

AF:

0.179

AC:

27270

AN:

152090

Hom.:

2605

Cov.:

AF XY:

0.183

AC XY:

13583

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.232

AC:

9634

AN:

41496

American (AMR)

AF:

0.183

AC:

2803

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

711

AN:

3470

East Asian (EAS)

AF:

0.137

AC:

707

AN:

5154

South Asian (SAS)

AF:

0.234

AC:

1131

AN:

4828

European-Finnish (FIN)

AF:

0.182

AC:

1930

AN:

10588

Middle Eastern (MID)

AF:

0.171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.145

AC:

9881

AN:

67940

Other (OTH)

AF:

0.181

AC:

383

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1213

2427

3640

4854

6067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.158

Hom.:

2817

Bravo

AF:

0.177

Asia WGS

AF:

0.210

AC:

729

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Feb 25, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypogonadotropic hypogonadism 8 with or without anosmia

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.3

(source)

DANN

Benign

0.44

PhyloP100

-1.9

PromoterAI

0.079

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over