19-917611-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032551.5(KISS1R):c.109C>T(p.Pro37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,415,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

KISS1R
NM_032551.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.449

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17635864).

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.109C>T	p.Pro37Ser	missense	Exon 1 of 5	NP_115940.2	Q969F8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KISS1R	ENST00000234371.10	TSL:1 MANE Select	c.109C>T	p.Pro37Ser	missense	Exon 1 of 5	ENSP00000234371.3	Q969F8
KISS1R	ENST00000909146.1		c.109C>T	p.Pro37Ser	missense	Exon 1 of 5	ENSP00000579205.1
KISS1R	ENST00000606939.2	TSL:5	c.109C>T	p.Pro37Ser	missense	Exon 1 of 4	ENSP00000475639.1	U3KQ86

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000587

AC:

AN:

170428

AF XY:

0.0000108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000759

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1415192

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32360

American (AMR)

AF:

0.00

AC:

AN:

38100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25358

East Asian (EAS)

AF:

0.0000268

AC:

AN:

37254

South Asian (SAS)

AF:

0.00

AC:

AN:

81342

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5540

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091100

Other (OTH)

AF:

0.00

AC:

AN:

58668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.43

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.5

PhyloP100

-0.45

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.040

Sift

Uncertain

0.010

Sift4G

Benign

0.12

Polyphen

0.13

Vest4

0.041

MutPred

0.31

Gain of glycosylation at P37 (P = 0.0212)

MVP

0.77

MPC

1.0

ClinPred

0.18

GERP RS

1.6

PromoterAI

-0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.34

Mutation Taster

=84/16

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over