dbSNP rs1047587176: KISS1R:p.Tyr80His (chr19-917740-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_032551.5(KISS1R):c.238T>C(p.Tyr80His) variant causes a missense change. The variant allele was found at a frequency of 0.00000623 in 1,604,188 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: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

KISS1R
NM_032551.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.92

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 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.912

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.238T>C	p.Tyr80His	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.238T>C	p.Tyr80His	missense	Exon 1 of 5	ENSP00000234371.3	Q969F8
KISS1R	ENST00000909146.1		c.238T>C	p.Tyr80His	missense	Exon 1 of 5	ENSP00000579205.1
KISS1R	ENST00000606939.2	TSL:5	c.238T>C	p.Tyr80His	missense	Exon 1 of 4	ENSP00000475639.1	U3KQ86

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

230480

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000482

AC:

AN:

1451978

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

721412

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32964

American (AMR)

AF:

0.00

AC:

AN:

44130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25922

East Asian (EAS)

AF:

0.00

AC:

AN:

39224

South Asian (SAS)

AF:

0.00

AC:

AN:

85324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00000632

AC:

AN:

1107426

Other (OTH)

AF:

0.00

AC:

AN:

59898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

AF:

0.0000197

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.43

MetaRNN

Pathogenic

0.91

MetaSVM

Uncertain

0.51

MutationAssessor

Pathogenic

4.0

PhyloP100

3.9

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-4.2

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.64

MutPred

0.78

Loss of stability (P = 0.1203)

MVP

0.98

MPC

2.2

ClinPred

1.0

GERP RS

3.9

PromoterAI

0.076

Neutral

(source)

Varity_R

0.93

gMVP

0.52

Mutation Taster

=39/61

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over