Genetic Variant GZMK:c.213-2036G>C (chr5-55028398-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.216

Publications

3 publications found

Variant links:

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]

GZMK links:

ENSG00000240535 (HGNC:):

ENSG00000240535 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GZMK	NM_002104.3	MANE Select	c.213-2036G>C		intron	N/A	NP_002095.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GZMK	ENST00000231009.3	TSL:1 MANE Select	c.213-2036G>C	intron	N/A	ENSP00000231009.2
ENSG00000240535	ENST00000615560.4	TSL:5	n.190C>G	non_coding_transcript_exon	Exon 1 of 5
ENSG00000240535	ENST00000595218.5	TSL:5	n.535+5338C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.659

AC:

100177

AN:

151964

Hom.:

34716

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.659

AC:

100294

AN:

152082

Hom.:

34768

Cov.:

AF XY:

0.662

AC XY:

49198

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.878

AC:

36456

AN:

41516

American (AMR)

AF:

0.685

AC:

10469

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.552

AC:

1917

AN:

3472

East Asian (EAS)

AF:

0.525

AC:

2710

AN:

5166

South Asian (SAS)

AF:

0.633

AC:

3049

AN:

4816

European-Finnish (FIN)

AF:

0.616

AC:

6494

AN:

10534

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.546

AC:

37133

AN:

67976

Other (OTH)

AF:

0.633

AC:

1336

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1599

3197

4796

6394

7993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

8.1

(source)

DANN

Benign

0.83

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over