19-917380-C-T

Position:

• chr19-917380-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032551.5(KISS1R):​c.-123C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,201,018 control chromosomes in the GnomAD database, including 536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (318 hom., cov: 33)
  • Exomes 𝑓: 0.0059 (218 hom.)
• Consequence: KISS1R NM_032551.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.51

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 19-917380-C-T is Benign according to our data. Variant chr19-917380-C-T is described in ClinVar as [Benign]. Clinvar id is 1239176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KISS1R	NM_032551.5	c.-123C>T		5_prime_UTR_variant	1/5	ENST00000234371.10	NP_115940.2
KISS1R	XM_047439545.1	c.-123C>T		5_prime_UTR_variant	1/4		XP_047295501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KISS1R	ENST00000234371	c.-123C>T		5_prime_UTR_variant	1/5	1	NM_032551.5	ENSP00000234371.3
KISS1R	ENST00000592648	c.-123C>T		5_prime_UTR_variant	1/2	5		ENSP00000467666.1

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5879 AN: 152150 Hom.: 316 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.00591 AC: 6196 AN: 1048758 Hom.: 218 Cov.: 15 AF XY: 0.00567 AC XY: 2893 AN XY: 510668

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00129

Gnomad4 EAS exome AF: 0.0544

Gnomad4 SAS exome AF: 0.00922

Gnomad4 FIN exome AF: 0.000447

Gnomad4 NFE exome AF: 0.00117

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.0387 AC: 5893 AN: 152260 Hom.: 318 Cov.: 33 AF XY: 0.0370 AC XY: 2757 AN XY: 74460

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0572

Gnomad4 SAS AF: 0.0130

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00157

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0203 Hom.: 20

Bravo AF: 0.0432

Asia WGS AF: 0.0380 AC: 131 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.3
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs3810423; hg19: chr19-917380;