Variant 19-917520-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_032551.5(KISS1R):c.18G>A(p.Thr6Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00038 in 1,501,158 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00038 ( 2 hom. )

Consequence

KISS1R
NM_032551.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.29

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 19-917520-G-A is Benign according to our data. Variant chr19-917520-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1590131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.3 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KISS1R	NM_032551.5 link	c.18G>A	p.Thr6Thr	synonymous_variant	1/5	ENST00000234371.10	NP_115940.2	Q969F8
KISS1R	XM_047439545.1 link	c.18G>A	p.Thr6Thr	synonymous_variant	1/4		XP_047295501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KISS1R	ENST00000234371.10 link	c.18G>A	p.Thr6Thr	synonymous_variant	1/5	1	NM_032551.5	ENSP00000234371.3	Q969F8
KISS1R	ENST00000606939.2 link	c.18G>A	p.Thr6Thr	synonymous_variant	1/4	5		ENSP00000475639.1	U3KQ86
KISS1R	ENST00000592648.1 link	c.18G>A	p.Thr6Thr	synonymous_variant	1/2	5		ENSP00000467666.1	K7EQ45

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00105

AC:

112

AN:

106278

Hom.:

AF XY:

0.00116

AC XY:

AN XY:

58484

show subpopulations

Gnomad AFR exome

AF:

0.000277

Gnomad AMR exome

AF:

0.0000976

Gnomad ASJ exome

AF:

0.0163

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000242

Gnomad OTH exome

AF:

0.000600

GnomAD4 exome

AF:

0.000380

AC:

512

AN:

1348966

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

269

AN XY:

663346

show subpopulations

Gnomad4 AFR exome

AF:

0.0000354

Gnomad4 AMR exome

AF:

0.0000948

Gnomad4 ASJ exome

AF:

0.0159

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000734

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.000381

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.00240

Hom.:

Bravo

AF:

0.000495

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

KISS1R-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 10, 2023

- -

Hypogonadotropic hypogonadism 8 with or without anosmia;C3805879:Central precocious puberty 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 14, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.3

DANN

Benign

0.83

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.3

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over