9-127264905-G-A

Position:

• chr9-127264905-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032293.5(GARNL3):​c.28G>A​(p.Val10Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: GARNL3 NM_032293.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22828868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARNL3	NM_032293.5	c.28G>A	p.Val10Met	missense_variant	1/28	ENST00000373387.9	NP_115669.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARNL3	ENST00000373387.9	c.28G>A	p.Val10Met	missense_variant	1/28	1	NM_032293.5	ENSP00000362485.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2024

The c.28G>A (p.V10M) alteration is located in exon 1 (coding exon 1) of the GARNL3 gene. This alteration results from a G to A substitution at nucleotide position 28, causing the valine (V) at amino acid position 10 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	0.25
BayesDel_addAF	Benign	0.00036	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.031	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.26
Sift	Benign	0.083	T
Sift4G	Benign	0.14	T
Polyphen		0.98	D
Vest4		0.18
MutPred		0.21		Loss of catalytic residue at V10 (P = 0.0331);
MVP		0.66
MPC		0.51
ClinPred		0.40	T
GERP RS		4.5
Varity_R		0.066
gMVP		0.19

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.

Other links and lift over

hg19: chr9-130027184;