Variant 2-85695345-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_006433.5(GNLY):c.78T>C(p.Pro26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,613,226 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 38 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 48 hom. )

Consequence

GNLY
NM_006433.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0240

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-85695345-T-C is Benign according to our data. Variant chr2-85695345-T-C is described in ClinVar as [Benign]. Clinvar id is 786859.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.024 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2061/152340) while in subpopulation AFR AF= 0.047 (1954/41574). AF 95% confidence interval is 0.0453. There are 38 homozygotes in gnomad4. There are 975 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNLY	NM_006433.5 linkuse as main transcript	c.78T>C	p.Pro26=	synonymous_variant	2/5	ENST00000263863.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNLY	ENST00000263863.9 linkuse as main transcript	c.78T>C	p.Pro26=	synonymous_variant	2/5	1	NM_006433.5	P2	P22749-1

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2047

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0468

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00350

AC:

879

AN:

251324

Hom.:

AF XY:

0.00230

AC XY:

313

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.0487

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00138

AC:

2010

AN:

1460886

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

817

AN XY:

726846

show subpopulations

Gnomad4 AFR exome

AF:

0.0502

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.00285

GnomAD4 genome

AF:

0.0135

AC:

2061

AN:

152340

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

975

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0470

Gnomad4 AMR

AF:

0.00496

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00656

Hom.:

Bravo

AF:

0.0153

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.2

DANN

Benign

0.51

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

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