chr5-55032127-G-T

Variant names:

• chr5-55032127-G-T
• rs2112938
• NM_002104.3:c.633+494G>T

Variant summary

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

The NM_002104.3(GZMK):​c.633+494G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,978 control chromosomes in the GnomAD database, including 7,868 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 0.29 (7868 hom., cov: 32)
• Consequence: GZMK NM_002104.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 6 publications found

Genes affected

GZMK (HGNC:4711): (granzyme K) This gene product is a member of a group of related serine proteases from the cytoplasmic granules of cytotoxic lymphocytes. Cytolytic T lymphocytes (CTL) and natural killer (NK) cells share the remarkable ability to recognize, bind, and lyse specific target cells. They are thought to protect their host by lysing cells bearing on their surface 'nonself' antigens, usually peptides or proteins resulting from infection by intracellular pathogens. The protein described here lacks consensus sequences for N-glycosylation present in other granzymes. [provided by RefSeq, Jul 2008]

ENSG00000240535 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GZMK	NM_002104.3	c.633+494G>T		intron_variant	Intron 4 of 4	ENST00000231009.3	NP_002095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GZMK	ENST00000231009.3	c.633+494G>T		intron_variant	Intron 4 of 4	1	NM_002104.3	ENSP00000231009.2

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44278 AN: 151860 Hom.: 7849 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.275

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44354 AN: 151978 Hom.: 7868 Cov.: 32 AF XY: 0.289 AC XY: 21445 AN XY: 74272

African (AFR) AF: 0.500 AC: 20689 AN: 41398

American (AMR) AF: 0.239 AC: 3652 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3468

East Asian (EAS) AF: 0.321 AC: 1658 AN: 5166

South Asian (SAS) AF: 0.160 AC: 768 AN: 4806

European-Finnish (FIN) AF: 0.200 AC: 2116 AN: 10562

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.206 AC: 13983 AN: 67978

Other (OTH) AF: 0.280 AC: 590 AN: 2108

Alfa AF: 0.224 Hom.: 5491

Bravo AF: 0.306

Asia WGS AF: 0.300 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.8
DANN	Benign	0.82
PhyloP100		1.4
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: rs2112938; hg19: chr5-54327955; COSMIC: COSV50244502; COSMIC: COSV50244502;