Variant 9-127342326-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032293.5(GARNL3):c.1243T>A(p.Leu415Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000448 in 1,599,414 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00044 ( 1 hom. )

Consequence

GARNL3
NM_032293.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.152

Variant links:

Genes affected

GARNL3 (HGNC:25425): (GTPase activating Rap/RanGAP domain like 3) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

GARNL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03742042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARNL3	NM_032293.5 link	c.1243T>A	p.Leu415Met	missense_variant	Exon 14 of 28	ENST00000373387.9	NP_115669.3	Q5VVW2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GARNL3	ENST00000373387.9 link	c.1243T>A	p.Leu415Met	missense_variant	Exon 14 of 28	1	NM_032293.5	ENSP00000362485.4	Q5VVW2-1
GARNL3	ENST00000435213.6 link	c.1177T>A	p.Leu393Met	missense_variant	Exon 15 of 29	2		ENSP00000396205.2	Q5VVW2-5
GARNL3	ENST00000373386.6 link	n.1189T>A		non_coding_transcript_exon_variant	Exon 14 of 27	2		ENSP00000362484.2	A0A0C4DFW0
GARNL3	ENST00000460176.6 link	n.10T>A		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000474589.1	S4R3P7

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000450

AC:

113

AN:

251348

Hom.:

AF XY:

0.000434

AC XY:

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000926

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000598

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000442

AC:

639

AN:

1447136

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

301

AN XY:

720962

show subpopulations

Gnomad4 AFR exome

AF:

0.0000905

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000512

Gnomad4 OTH exome

AF:

0.000284

GnomAD4 genome

AF:

0.000506

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000508

Hom.:

Bravo

AF:

0.000623

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000338

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

The c.1243T>A (p.L415M) alteration is located in exon 14 (coding exon 14) of the GARNL3 gene. This alteration results from a T to A substitution at nucleotide position 1243, causing the leucine (L) at amino acid position 415 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.021

.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-0.41

MutationAssessor

Benign

-0.41

.;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.0

N;N

REVEL

Benign

0.21

Sift

Benign

0.25

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.17

.;B

Vest4

0.43

MVP

0.55

MPC

0.46

ClinPred

0.016

GERP RS

0.24

Varity_R

0.083

gMVP

0.34

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