5-55028794-T-C

Position:

• chr5-55028794-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002104.3(GZMK):​c.213-1640T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,082 control chromosomes in the GnomAD database, including 17,434 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 0.44 (17434 hom., cov: 33)
• Consequence: GZMK NM_002104.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GZMK	NM_002104.3	c.213-1640T>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.213-1640T>C		intron_variant		1	NM_002104.3	ENSP00000231009	P1
	ENST00000609699.5	n.1339-1798A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66798 AN: 151964 Hom.: 17393 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.440 AC: 66914 AN: 152082 Hom.: 17434 Cov.: 33 AF XY: 0.438 AC XY: 32549 AN XY: 74370

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.437

Alfa AF: 0.325 Hom.: 16756

Bravo AF: 0.466

Asia WGS AF: 0.385 AC: 1336 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	1.3
DANN	Benign	0.68

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: rs6875661; hg19: chr5-54324622; COSMIC: COSV50244487; COSMIC: COSV50244487;