chrX-48771050-G-A

Position:

• chrX-48771050-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080489.3(GLOD5):​c.325G>A​(p.Val109Met) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: GLOD5 NM_001080489.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.314

Genes affected

GLOD5 (HGNC:33358): (glyoxalase domain containing 5) This gene encodes a protein with a glyoxalase domain. [provided by RefSeq, Sep 2011]

ACMG classification

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=0.059285164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLOD5	NM_001080489.3	c.325G>A	p.Val109Met	missense_variant	3/4	ENST00000303227.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLOD5	ENST00000303227.11	c.325G>A	p.Val109Met	missense_variant	3/4	5	NM_001080489.3	P1
GLOD5	ENST00000445229.1	c.226G>A	p.Val76Met	missense_variant	2/3	2
GLOD5	ENST00000470676.1	n.321G>A		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 22

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

Dec 20, 2023

The c.325G>A (p.V109M) alteration is located in exon 3 (coding exon 3) of the GLOD5 gene. This alteration results from a G to A substitution at nucleotide position 325, causing the valine (V) at amino acid position 109 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	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T
FATHMM_MKL	Benign	0.015	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.033
Sift	Benign	0.34	T
Sift4G	Benign	0.27	T
Vest4		0.12
MVP		0.53
MPC		0.011
ClinPred		0.037	T
GERP RS		-0.58
Varity_R		0.22
gMVP		0.38

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: chrX-48629466;