6-31588932-A-G

Variant names:

• chr6-31588932-A-G
• rs986475
• NM_147130.3:c.*135T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_147130.3(NCR3):​c.*135T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 1,028,844 control chromosomes in the GnomAD database, including 5,844 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.088 (867 hom., cov: 32)
  • Exomes 𝑓: 0.093 (4977 hom.)
• Consequence: NCR3 NM_147130.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 50 publications found

Genes affected

NCR3 (HGNC:19077): (natural cytotoxicity triggering receptor 3) The protein encoded by this gene is a natural cytotoxicity receptor (NCR) that may aid NK cells in the lysis of tumor cells. The encoded protein interacts with CD3-zeta (CD247), a T-cell receptor. A single nucleotide polymorphism in the 5' untranslated region of this gene has been associated with mild malaria suceptibility. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

LST1 (HGNC:14189): (leukocyte specific transcript 1) The protein encoded by this gene is a membrane protein that can inhibit the proliferation of lymphocytes. Expression of this gene is enhanced by lipopolysaccharide, interferon-gamma, and bacteria. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147130.3. 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
	NCR3	NM_147130.3	MANE Select	c.*135T>C		3_prime_UTR	Exon 4 of 4	NP_667341.1	O14931-1
	NCR3	NM_001145466.2		c.*262T>C		3_prime_UTR	Exon 4 of 4	NP_001138938.1	Q05D23
	LST1	NM_205839.3	MANE Select	c.*256A>G		downstream_gene	N/A	NP_995311.2	O00453-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCR3	ENST00000340027.10	TSL:1 MANE Select	c.*135T>C		3_prime_UTR	Exon 4 of 4	ENSP00000342156.5	O14931-1
	NCR3	ENST00000376073.8	TSL:1	c.*262T>C		3_prime_UTR	Exon 4 of 4	ENSP00000365241.4	O14931-3
	NCR3	ENST00000934501.1		c.*135T>C		3_prime_UTR	Exon 5 of 5	ENSP00000604560.1

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13423 AN: 152146 Hom.: 864 Cov.: 32

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.0966

GnomAD4 exome AF: 0.0928 AC: 81309 AN: 876580 Hom.: 4977 Cov.: 12 AF XY: 0.0958 AC XY: 41842 AN XY: 436990

African (AFR) AF: 0.0329 AC: 657 AN: 19990

American (AMR) AF: 0.208 AC: 3972 AN: 19094

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 3705 AN: 16186

East Asian (EAS) AF: 0.198 AC: 6524 AN: 32870

South Asian (SAS) AF: 0.138 AC: 7138 AN: 51578

European-Finnish (FIN) AF: 0.0553 AC: 2466 AN: 44620

Middle Eastern (MID) AF: 0.153 AC: 430 AN: 2816

European-Non Finnish (NFE) AF: 0.0807 AC: 52407 AN: 649444

Other (OTH) AF: 0.100 AC: 4010 AN: 39982

GnomAD4 genome AF: 0.0883 AC: 13445 AN: 152264 Hom.: 867 Cov.: 32 AF XY: 0.0905 AC XY: 6738 AN XY: 74446

African (AFR) AF: 0.0299 AC: 1243 AN: 41560

American (AMR) AF: 0.179 AC: 2743 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3472

East Asian (EAS) AF: 0.155 AC: 803 AN: 5178

South Asian (SAS) AF: 0.134 AC: 646 AN: 4826

European-Finnish (FIN) AF: 0.0555 AC: 589 AN: 10610

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0916 AC: 6228 AN: 68008

Other (OTH) AF: 0.102 AC: 216 AN: 2114

Alfa AF: 0.0954 Hom.: 2421

Bravo AF: 0.0940

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.59
PhyloP100		0.069
Mutation Taster		=100/0	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: rs986475; hg19: chr6-31556709;