chr19-917380-C-T

Variant names:

• chr19-917380-C-T
• rs3810423
• NM_032551.5:c.-123C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 VariationId 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.

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.-123C>T		5_prime_UTR	Exon 1 of 5	NP_115940.2	Q969F8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KISS1R	ENST00000234371.10	TSL:1 MANE Select	c.-123C>T		5_prime_UTR	Exon 1 of 5	ENSP00000234371.3	Q969F8
	KISS1R	ENST00000909146.1		c.-123C>T		5_prime_UTR	Exon 1 of 5	ENSP00000579205.1
	KISS1R	ENST00000592648.1	TSL:5	c.-123C>T		5_prime_UTR	Exon 1 of 2	ENSP00000467666.1	K7EQ45

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

African (AFR) AF: 0.126 AC: 2558 AN: 20364

American (AMR) AF: 0.0107 AC: 107 AN: 9996

Ashkenazi Jewish (ASJ) AF: 0.00129 AC: 20 AN: 15494

East Asian (EAS) AF: 0.0544 AC: 1478 AN: 27180

South Asian (SAS) AF: 0.00922 AC: 428 AN: 46424

European-Finnish (FIN) AF: 0.000447 AC: 13 AN: 29064

Middle Eastern (MID) AF: 0.00816 AC: 25 AN: 3062

European-Non Finnish (NFE) AF: 0.00117 AC: 998 AN: 852890

Other (OTH) AF: 0.0128 AC: 569 AN: 44284

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

African (AFR) AF: 0.124 AC: 5140 AN: 41538

American (AMR) AF: 0.0140 AC: 215 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.0572 AC: 296 AN: 5172

South Asian (SAS) AF: 0.0130 AC: 63 AN: 4832

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10614

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00157 AC: 107 AN: 68016

Other (OTH) AF: 0.0284 AC: 60 AN: 2112

Alfa AF: 0.0203 Hom.: 20

Bravo AF: 0.0432

Asia WGS AF: 0.0380 AC: 131 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.3
DANN	Benign	0.70
PhyloP100		-1.5
PromoterAI		0.065	Neutral
Mutation Taster		=300/0	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: rs3810423; hg19: chr19-917380;