chr14-24607157-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_033423.5(GZMH):c.589G>A(p.Gly197Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,611,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

GZMH
NM_033423.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.08

Publications

0 publications found

Variant links:

Genes affected

GZMH (HGNC:4710): (granzyme H) This gene encodes a member of the peptidase S1 family of serine proteases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate a chymotrypsin-like protease. This protein is reported to be constitutively expressed in the NK (natural killer) cells of the immune system and may play a role in the cytotoxic arm of the innate immune response by inducing target cell death and by directly cleaving substrates in pathogen-infected cells. This gene is present in a gene cluster with another member of the granzyme subfamily on chromosome 14. [provided by RefSeq, Nov 2015]

GZMH links:

GZMH-AS1 (HGNC:58166):

GZMH-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031519026).

BP6

Variant 14-24607157-C-T is Benign according to our data. Variant chr14-24607157-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3856464.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033423.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GZMH	NM_033423.5	MANE Select	c.589G>A	p.Gly197Ser	missense	Exon 4 of 5	NP_219491.1	P20718-1
GZMH	NM_001270780.2		c.405+184G>A		intron	N/A	NP_001257709.1
GZMH	NM_001270781.2		c.340-411G>A		intron	N/A	NP_001257710.1	P20718-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GZMH	ENST00000216338.9	TSL:1 MANE Select	c.589G>A	p.Gly197Ser	missense	Exon 4 of 5	ENSP00000216338.4	P20718-1
GZMH	ENST00000382548.4	TSL:1	c.340-411G>A		intron	N/A	ENSP00000371988.4	P20718-2
GZMH	ENST00000557220.6	TSL:1	c.205-411G>A		intron	N/A	ENSP00000450576.2	A0A0C4DGJ9

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000241

AC:

AN:

248884

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000254

AC:

AN:

1459406

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

725602

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39624

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53312

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000261

AC:

AN:

1110308

Other (OTH)

AF:

0.0000829

AC:

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41434

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.585

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000565

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.0020

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.14

Eigen

Benign

-2.5

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.092

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.70

MutationAssessor

Benign

-1.5

PhyloP100

-8.1

PrimateAI

Benign

0.24

PROVEAN

Benign

1.5

REVEL

Benign

0.25

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.030

Vest4

0.088

MVP

0.42

MPC

0.11

ClinPred

0.039

GERP RS

-9.5

Varity_R

0.15

gMVP

0.43

Mutation Taster

=99/1

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over