Variant 9-127342287-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032293.5(GARNL3):c.1204A>G(p.Met402Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GARNL3
NM_032293.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARNL3	NM_032293.5 link	c.1204A>G	p.Met402Val	missense_variant	14/28	ENST00000373387.9	NP_115669.3	Q5VVW2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GARNL3	ENST00000373387.9 link	c.1204A>G	p.Met402Val	missense_variant	14/28	1	NM_032293.5	ENSP00000362485.4	Q5VVW2-1
GARNL3	ENST00000435213.6 link	c.1138A>G	p.Met380Val	missense_variant	15/29	2		ENSP00000396205.2	Q5VVW2-5
GARNL3	ENST00000373386.6 link	n.1150A>G		non_coding_transcript_exon_variant	14/27	2		ENSP00000362484.2	A0A0C4DFW0
GARNL3	ENST00000460176.6 link	n.-30A>G		upstream_gene_variant		5		ENSP00000474589.1	S4R3P7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727204

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 21, 2024

The c.1204A>G (p.M402V) alteration is located in exon 14 (coding exon 14) of the GARNL3 gene. This alteration results from a A to G substitution at nucleotide position 1204, causing the methionine (M) at amino acid position 402 to be replaced by a valine (V). 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

Pathogenic

0.71

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.080

.;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

M_CAP

Pathogenic

0.47

MetaRNN

Pathogenic

0.85

D;D

MetaSVM

Pathogenic

0.80

MutationAssessor

Uncertain

2.4

.;M

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.3

N;N

REVEL

Pathogenic

0.76

Sift

Benign

0.082

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.97

.;D

Vest4

0.87

MutPred

0.47

.;Loss of disorder (P = 0.0547);

MVP

0.77

MPC

0.66

ClinPred

0.95

GERP RS

5.4

Varity_R

0.34

gMVP

0.64

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