5-55028398-G-C

Position:

• chr5-55028398-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002104.3(GZMK):​c.213-2036G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,082 control chromosomes in the GnomAD database, including 34,768 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 0.66 (34768 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GZMK NM_002104.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GZMK	NM_002104.3	c.213-2036G>C		intron_variant		ENST00000231009.3	NP_002095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GZMK	ENST00000231009.3	c.213-2036G>C		intron_variant		1	NM_002104.3	ENSP00000231009.2

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100177 AN: 151964 Hom.: 34716 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.631

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.659 AC: 100294 AN: 152082 Hom.: 34768 Cov.: 32 AF XY: 0.662 AC XY: 49198 AN XY: 74326

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.633

Alfa AF: 0.436 Hom.: 1041

Bravo AF: 0.676

Asia WGS AF: 0.620 AC: 2156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	8.1
DANN	Benign	0.83

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: rs3776038; hg19: chr5-54324226; COSMIC: COSV50244484; COSMIC: COSV50244484;