5-55028794-T-C

Variant names:

• chr5-55028794-T-C
• rs6875661
• NM_002104.3:c.213-1640T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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 = 0.722 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002104.3. 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
	GZMK	NM_002104.3	MANE Select	c.213-1640T>C		intron	N/A	NP_002095.1	P49863

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GZMK	ENST00000231009.3	TSL:1 MANE Select	c.213-1640T>C		intron	N/A	ENSP00000231009.2	P49863
	ENSG00000240535	ENST00000595218.5	TSL:5	n.535+4942A>G		intron	N/A
	ENSG00000240535	ENST00000596137.5	TSL:5	n.96-488A>G		intron	N/A

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

African (AFR) AF: 0.729 AC: 30243 AN: 41496

American (AMR) AF: 0.450 AC: 6877 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1255 AN: 3466

East Asian (EAS) AF: 0.348 AC: 1803 AN: 5176

South Asian (SAS) AF: 0.277 AC: 1338 AN: 4832

European-Finnish (FIN) AF: 0.326 AC: 3438 AN: 10554

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20609 AN: 67976

Other (OTH) AF: 0.437 AC: 923 AN: 2112

Alfa AF: 0.347 Hom.: 42143

Bravo AF: 0.466

Asia WGS AF: 0.385 AC: 1336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-0.12
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: rs6875661; hg19: chr5-54324622; COSMIC: COSV50244487; COSMIC: COSV50244487;