11-17372437-ACCT-A

Position:

• chr11-17372437-ACCT-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001202439.3(NCR3LG1):​c.1296_1298delTCC​(p.Pro433del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00276 in 703,126 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (5 hom.)
• Consequence: NCR3LG1 NM_001202439.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.206

Genes affected

NCR3LG1 (HGNC:42400): (natural killer cell cytotoxicity receptor 3 ligand 1) B7H6 belongs to the B7 family (see MIM 605402) and is selectively expressed on tumor cells. Interaction of B7H6 with NKp30 (NCR3; MIM 611550) results in natural killer (NK) cell activation and cytotoxicity (Brandt et al., 2009 [PubMed 19528259]).[supplied by OMIM, Jan 2011]

KCNJ11 (HGNC:6257): (potassium inwardly rectifying channel subfamily J member 11) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and is found associated with the sulfonylurea receptor SUR. Mutations in this gene are a cause of familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion. Defects in this gene may also contribute to autosomal dominant non-insulin-dependent diabetes mellitus type II (NIDDM), transient neonatal diabetes mellitus type 3 (TNDM3), and permanent neonatal diabetes mellitus (PNDM). Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 11-17372437-ACCT-A is Benign according to our data. Variant chr11-17372437-ACCT-A is described in ClinVar as [Likely_benign]. Clinvar id is 3388185.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCR3LG1	NM_001202439.3	c.1296_1298delTCC	p.Pro433del	disruptive_inframe_deletion	5/5	ENST00000338965.9	NP_001189368.1
NCR3LG1	XM_047426906.1	c.1296_1298delTCC	p.Pro433del	disruptive_inframe_deletion	5/6		XP_047282862.1
NCR3LG1	XM_011520074.4	c.1209_1211delTCC	p.Pro404del	disruptive_inframe_deletion	5/5		XP_011518376.1
NCR3LG1	XM_011520075.4	c.1209_1211delTCC	p.Pro404del	disruptive_inframe_deletion	5/5		XP_011518377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCR3LG1	ENST00000338965.9	c.1296_1298delTCC	p.Pro433del	disruptive_inframe_deletion	5/5	1	NM_001202439.3	ENSP00000341637.4
KCNJ11	ENST00000682764.1	c.*51-6138_*51-6136delAGG		intron_variant				ENSP00000506780.1
NCR3LG1	ENST00000530403.1	n.1296_1298delTCC		non_coding_transcript_exon_variant	5/6	5		ENSP00000434394.1

Frequencies

GnomAD3 genomes AF: 0.00264 AC: 401 AN: 152020 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000849

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00482

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00232 AC: 321 AN: 138140 Hom.: 0 AF XY: 0.00245 AC XY: 183 AN XY: 74710

Gnomad AFR exome AF: 0.000595

Gnomad AMR exome AF: 0.000694

Gnomad ASJ exome AF: 0.000120

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00160

Gnomad FIN exome AF: 0.00100

Gnomad NFE exome AF: 0.00452

Gnomad OTH exome AF: 0.00235

GnomAD4 exome AF: 0.00279 AC: 1540 AN: 550988 Hom.: 5 AF XY: 0.00267 AC XY: 795 AN XY: 298254

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.000806

Gnomad4 ASJ exome AF: 0.0000999

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00183

Gnomad4 FIN exome AF: 0.000919

Gnomad4 NFE exome AF: 0.00398

Gnomad4 OTH exome AF: 0.00267

GnomAD4 genome AF: 0.00264 AC: 401 AN: 152138 Hom.: 1 Cov.: 32 AF XY: 0.00237 AC XY: 176 AN XY: 74368

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000849

Gnomad4 NFE AF: 0.00482

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00247 Hom.: 0

Bravo AF: 0.00254

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

NCR3LG1: PM4:Supporting, BS2 -

Computational scores

Source: dbNSFP v4.3

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: rs567313382; hg19: chr11-17393984;