rs10407968

Variant names:

• chr19-917526-A-G
• rs10407968
• NM_032551.5:c.24A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.89
• Publications: 18 publications found

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

ACMG classification

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.

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.24A>G	p.Gly8Gly	synonymous	Exon 1 of 5	NP_115940.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KISS1R	ENST00000234371.10	TSL:1 MANE Select	c.24A>G	p.Gly8Gly	synonymous	Exon 1 of 5	ENSP00000234371.3
	KISS1R	ENST00000909146.1		c.24A>G	p.Gly8Gly	synonymous	Exon 1 of 5	ENSP00000579205.1
	KISS1R	ENST00000606939.2	TSL:5	c.24A>G	p.Gly8Gly	synonymous	Exon 1 of 4	ENSP00000475639.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27245 AN: 151980 Hom.: 2595 Cov.: 33

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

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.: 32 AF XY: 0.149 AC XY: 99287 AN XY: 664556

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

GnomAD4 genome AF: 0.179 AC: 27270 AN: 152090 Hom.: 2605 Cov.: 33 AF XY: 0.183 AC XY: 13583 AN XY: 74360

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: 50 AN: 292

European-Non Finnish (NFE) AF: 0.145 AC: 9881 AN: 67940

Other (OTH) AF: 0.181 AC: 383 AN: 2112

Alfa AF: 0.158 Hom.: 2817

Bravo AF: 0.177

Asia WGS AF: 0.210 AC: 729 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Hypogonadotropic hypogonadism 8 with or without anosmia (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.44
PhyloP100		-1.9
PromoterAI		0.079	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10407968; hg19: chr19-917526;