11-17356708-A-G

Variant names:

• chr11-17356708-A-G
• rs760833393
• NM_001202439.3:c.128A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001202439.3(NCR3LG1):​c.128A>G​(p.Asn43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000872 in 1,536,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000087 (0 hom.)
• Consequence: NCR3LG1 NM_001202439.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.153
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.036564946).
• BP6: Variant 11-17356708-A-G is Benign according to our data. Variant chr11-17356708-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3298941.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCR3LG1	NM_001202439.3	c.128A>G	p.Asn43Ser	missense_variant	Exon 2 of 5	ENST00000338965.9	NP_001189368.1
NCR3LG1	XM_047426906.1	c.128A>G	p.Asn43Ser	missense_variant	Exon 2 of 6		XP_047282862.1
NCR3LG1	XM_011520074.4	c.41A>G	p.Asn14Ser	missense_variant	Exon 2 of 5		XP_011518376.1
NCR3LG1	XM_011520075.4	c.41A>G	p.Asn14Ser	missense_variant	Exon 2 of 5		XP_011518377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCR3LG1	ENST00000338965.9	c.128A>G	p.Asn43Ser	missense_variant	Exon 2 of 5	1	NM_001202439.3	ENSP00000341637.4
NCR3LG1	ENST00000530403.1	n.128A>G		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000434394.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152192 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.0000712 AC: 10 AN: 140546 AF XY: 0.0000922

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.000470

GnomAD4 exome AF: 0.0000867 AC: 120 AN: 1384070 Hom.: 0 Cov.: 31 AF XY: 0.0000966 AC XY: 66 AN XY: 682958

African (AFR) AF: 0.0000316 AC: 1 AN: 31596

American (AMR) AF: 0.0000280 AC: 1 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35734

South Asian (SAS) AF: 0.0000631 AC: 5 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34008

Middle Eastern (MID) AF: 0.000702 AC: 4 AN: 5698

European-Non Finnish (NFE) AF: 0.0000918 AC: 99 AN: 1078950

Other (OTH) AF: 0.000138 AC: 8 AN: 57968

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152192 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.000458 AC: 7 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.000102 AC: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 20, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.27
DANN	Benign	0.51
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.020	N
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.15
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.0060
Sift	Benign	0.31	T
Sift4G	Benign	0.21	T
Polyphen		0.023	B
Vest4		0.10
MutPred		0.41		Loss of stability (P = 0.1153);
MVP		0.040
ClinPred		0.011	T
GERP RS		1.5
Varity_R		0.14
gMVP		0.22
Mutation Taster		=99/1	polymorphism

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: rs760833393; hg19: chr11-17378255;