rs6875666

Variant names:

• chr5-55028806-T-A
• rs6875666
• NM_002104.3:c.213-1628T>A

Variant summary

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

The NM_002104.3(GZMK):​c.213-1628T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,122 control chromosomes in the GnomAD database, including 19,381 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 0.46 (19381 hom., cov: 33)
• Consequence: GZMK NM_002104.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GZMK	NM_002104.3	c.213-1628T>A		intron_variant	Intron 2 of 4	ENST00000231009.3	NP_002095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GZMK	ENST00000231009.3	c.213-1628T>A		intron_variant	Intron 2 of 4	1	NM_002104.3	ENSP00000231009.2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69357 AN: 152004 Hom.: 19324 Cov.: 33

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.457 AC: 69490 AN: 152122 Hom.: 19381 Cov.: 33 AF XY: 0.454 AC XY: 33745 AN XY: 74372

African (AFR) AF: 0.789 AC: 32759 AN: 41502

American (AMR) AF: 0.455 AC: 6954 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1256 AN: 3468

East Asian (EAS) AF: 0.341 AC: 1764 AN: 5180

South Asian (SAS) AF: 0.277 AC: 1336 AN: 4830

European-Finnish (FIN) AF: 0.325 AC: 3436 AN: 10562

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

European-Non Finnish (NFE) AF: 0.303 AC: 20606 AN: 67982

Other (OTH) AF: 0.450 AC: 951 AN: 2112

Alfa AF: 0.387 Hom.: 1723

Bravo AF: 0.485

Asia WGS AF: 0.387 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.51
PhyloP100		-0.89
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: rs6875666; hg19: chr5-54324634; COSMIC: COSV50244490; COSMIC: COSV50244490;