X-48770948-T-G

Position:

• chrX-48770948-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001080489.3(GLOD5):​c.223T>G​(p.Phe75Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000179 in 111,600 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 22)
• Consequence: GLOD5 NM_001080489.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.61

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 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, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLOD5	NM_001080489.3	c.223T>G	p.Phe75Val	missense_variant	3/4	ENST00000303227.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLOD5	ENST00000303227.11	c.223T>G	p.Phe75Val	missense_variant	3/4	5	NM_001080489.3	P1
GLOD5	ENST00000445229.1	c.124T>G	p.Phe42Val	missense_variant	2/3	2
GLOD5	ENST00000470676.1	n.219T>G		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111600 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33784

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000192

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111600 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33784

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000192

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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

Mar 21, 2023

The c.223T>G (p.F75V) alteration is located in exon 3 (coding exon 3) of the GLOD5 gene. This alteration results from a T to G substitution at nucleotide position 223, causing the phenylalanine (F) at amino acid position 75 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	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	-0.045	T
MutationAssessor	Pathogenic	3.7	H
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Pathogenic	0.90
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.027	D
Vest4		0.82
MVP		0.66
MPC		0.074
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.96
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1557017299; hg19: chrX-48629364;