Variant 2-85694429-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_006433.5(GNLY):c.11G>A(p.Trp4Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,614,064 control chromosomes in the GnomAD database, including 288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 141 hom., cov: 34)

Exomes 𝑓: 0.0025 ( 147 hom. )

Consequence

GNLY
NM_006433.5 stop_gained

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: 0.359

Variant links:

Genes affected

GNLY (HGNC:4414): (granulysin) The product of this gene is a member of the saposin-like protein (SAPLIP) family and is located in the cytotoxic granules of T cells, which are released upon antigen stimulation. This protein is present in cytotoxic granules of cytotoxic T lymphocytes and natural killer cells, and it has antimicrobial activity against M. tuberculosis and other organisms. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

GNLY links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM4

Stoplost variant in NM_006433.5 Downstream stopcodon found after 165 codons.

BP6

Variant 2-85694429-G-A is Benign according to our data. Variant chr2-85694429-G-A is described in ClinVar as [Benign]. Clinvar id is 780828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNLY	NM_006433.5 linkuse as main transcript	c.11G>A	p.Trp4Ter	stop_gained	1/5	ENST00000263863.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNLY	ENST00000263863.9 linkuse as main transcript	c.11G>A	p.Trp4Ter	stop_gained	1/5	1	NM_006433.5	P2	P22749-1

Frequencies

GnomAD3 genomes

AF:

0.0240

AC:

3657

AN:

152236

Hom.:

140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0839

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00824

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.00643

AC:

1615

AN:

250998

Hom.:

AF XY:

0.00482

AC XY:

654

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.0886

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00247

AC:

3615

AN:

1461708

Hom.:

147

Cov.:

AF XY:

0.00210

AC XY:

1527

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.0892

Gnomad4 AMR exome

AF:

0.00467

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.00553

GnomAD4 genome

AF:

0.0240

AC:

3653

AN:

152356

Hom.:

141

Cov.:

AF XY:

0.0233

AC XY:

1737

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0836

Gnomad4 AMR

AF:

0.00810

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00643

Hom.:

Bravo

AF:

0.0279

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0810

AC:

357

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00762

AC:

925

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Uncertain significance, no assertion criteria provided	literature only	OMIM	Mar 09, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 20, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 28, 2020	This variant is associated with the following publications: (PMID: 31642954) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.22

Cadd

Pathogenic

Dann

Benign

0.97

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.012

MutationTaster

Benign

1.0

A;A;N

Vest4

0.60

GERP RS

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over