Variant 19-917669-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032551.5(KISS1R):c.167G>A(p.Gly56Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,126 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KISS1R
NM_032551.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KISS1R	NM_032551.5 linkuse as main transcript	c.167G>A	p.Gly56Asp	missense_variant	1/5	ENST00000234371.10	NP_115940.2	Q969F8
KISS1R	XM_047439545.1 linkuse as main transcript	c.167G>A	p.Gly56Asp	missense_variant	1/4		XP_047295501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KISS1R	ENST00000234371.10 linkuse as main transcript	c.167G>A	p.Gly56Asp	missense_variant	1/5	1	NM_032551.5	ENSP00000234371.3	Q969F8
KISS1R	ENST00000606939.2 linkuse as main transcript	c.167G>A	p.Gly56Asp	missense_variant	1/4	5		ENSP00000475639.1	U3KQ86
KISS1R	ENST00000592648.1 linkuse as main transcript	c.167G>A	p.Gly56Asp	missense_variant	1/2	5		ENSP00000467666.1	K7EQ45

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000476

AC:

AN:

209864

Hom.:

AF XY:

0.00

AC XY:

AN XY:

114690

show subpopulations

Gnomad AFR exome

AF:

0.0000793

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443126

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716586

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000669

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 21, 2022

The c.167G>A (p.G56D) alteration is located in exon 1 (coding exon 1) of the KISS1R gene. This alteration results from a G to A substitution at nucleotide position 167, causing the glycine (G) at amino acid position 56 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.053

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

.;D;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.0049

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.78

D;D;D

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.8

.;M;.

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-5.8

.;D;.

REVEL

Uncertain

0.38

Sift

Uncertain

0.0020

.;D;.

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.77, 0.80

MVP

0.89

MPC

2.1

ClinPred

0.97

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.95

gMVP

0.84

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