Variant 9-127344333-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032293.5(GARNL3):c.1350A>G(p.Ile450Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GARNL3
NM_032293.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.214

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.409034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARNL3	NM_032293.5 link	c.1350A>G	p.Ile450Met	missense_variant	15/28	ENST00000373387.9	NP_115669.3	Q5VVW2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GARNL3	ENST00000373387.9 link	c.1350A>G	p.Ile450Met	missense_variant	15/28	1	NM_032293.5	ENSP00000362485.4	Q5VVW2-1
GARNL3	ENST00000435213.6 link	c.1284A>G	p.Ile428Met	missense_variant	16/29	2		ENSP00000396205.2	Q5VVW2-5
GARNL3	ENST00000373386.6 link	n.1296A>G		non_coding_transcript_exon_variant	15/27	2		ENSP00000362484.2	A0A0C4DFW0
GARNL3	ENST00000460176.6 link	n.117A>G		non_coding_transcript_exon_variant	2/6	5		ENSP00000474589.1	S4R3P7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458536

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725792

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 09, 2024

The c.1350A>G (p.I450M) alteration is located in exon 15 (coding exon 15) of the GARNL3 gene. This alteration results from a A to G substitution at nucleotide position 1350, causing the isoleucine (I) at amino acid position 450 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

0.10

BayesDel_addAF

Uncertain

0.066

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

.;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.064

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.81

.;L

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.49

Sift

Uncertain

0.014

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.71

.;P

Vest4

0.59

MutPred

0.33

.;Gain of loop (P = 0.0195);

MVP

0.61

MPC

0.69

ClinPred

0.76

GERP RS

-1.2

Varity_R

0.27

gMVP

0.43

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over