Variant chr5-157162649-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_130899.3(GARIN3):c.1616G>A(p.Arg539Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,614,138 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 20 hom. )

Consequence

GARIN3
NM_130899.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.203

Variant links:

Genes affected

GARIN3 (HGNC:28397): (golgi associated RAB2 interactor family member 3) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

GARIN3 links:

ITK (HGNC:6171): (IL2 inducible T cell kinase) This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. It is thought to play a role in T-cell proliferation and differentiation. [provided by RefSeq, Jul 2008]

ITK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002883494).

BP6

Variant 5-157162649-C-T is Benign according to our data. Variant chr5-157162649-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2655990.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00316 (4626/1461890) while in subpopulation MID AF= 0.0229 (132/5768). AF 95% confidence interval is 0.0197. There are 20 homozygotes in gnomad4_exome. There are 2397 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARIN3	NM_130899.3 linkuse as main transcript	c.1616G>A	p.Arg539Lys	missense_variant	2/2	ENST00000302938.4	NP_570969.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARIN3	ENST00000302938.4 linkuse as main transcript	c.1616G>A	p.Arg539Lys	missense_variant	2/2	1	NM_130899.3	ENSP00000305596	P1
ITK	ENST00000521769.5 linkuse as main transcript	c.-296-3439C>T		intron_variant		4		ENSP00000430327

Frequencies

GnomAD3 genomes

AF:

0.00283

AC:

431

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00432

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00299

AC:

752

AN:

251268

Hom.:

AF XY:

0.00341

AC XY:

463

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00794

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00433

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00316

AC:

4626

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00330

AC XY:

2397

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.00803

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00210

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00335

Gnomad4 OTH exome

AF:

0.00412

GnomAD4 genome

AF:

0.00283

AC:

431

AN:

152248

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

190

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00432

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.00294

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00315

AC:

383

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00578

EpiControl

AF:

0.00747

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

GARIN3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.94

DANN

Benign

0.87

DEOGEN2

Benign

0.018

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.45

M_CAP

Benign

0.0036

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.1

REVEL

Benign

0.072

Sift

Benign

0.040

Sift4G

Uncertain

0.049

Polyphen

0.43

Vest4

0.11

MVP

0.28

MPC

0.11

ClinPred

0.0026

GERP RS

-0.24

Varity_R

0.12

gMVP

0.35

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