chr19-917735-A-C

Variant names:

• chr19-917735-A-C
• NM_032551.5:c.233A>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032551.5(KISS1R):​c.233A>C​(p.Asn78Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,454,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KISS1R NM_032551.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.06

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KISS1R	NM_032551.5	c.233A>C	p.Asn78Thr	missense_variant	Exon 1 of 5	ENST00000234371.10	NP_115940.2
KISS1R	XM_047439545.1	c.233A>C	p.Asn78Thr	missense_variant	Exon 1 of 4		XP_047295501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KISS1R	ENST00000234371.10	c.233A>C	p.Asn78Thr	missense_variant	Exon 1 of 5	1	NM_032551.5	ENSP00000234371.3
KISS1R	ENST00000606939.2	c.233A>C	p.Asn78Thr	missense_variant	Exon 1 of 4	5		ENSP00000475639.1
KISS1R	ENST00000592648.1	c.233A>C	p.Asn78Thr	missense_variant	Exon 1 of 2	5		ENSP00000467666.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454216 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722796

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	0.0063	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.58	.;D;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.7	.;H;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.1	.;D;.
REVEL	Uncertain	0.45
Sift	Uncertain	0.0030	.;D;.
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.70, 0.71
MutPred		0.93		Gain of glycosylation at N78 (P = 0.0151);Gain of glycosylation at N78 (P = 0.0151);Gain of glycosylation at N78 (P = 0.0151);
MVP		0.92
MPC		1.1
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.96
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-917735;