chr17-769898-C-T

Variant names:

• chr17-769898-C-T
• rs746588800
• NM_016080.4:c.802G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016080.4(GLOD4):​c.802G>A​(p.Asp268Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D268Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLOD4 NM_016080.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.50
• Publications: 0 publications found

Genes affected

GLOD4 (HGNC:14111): (glyoxalase domain containing 4) Enables cadherin binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016080.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLOD4	NM_016080.4	MANE Select	c.802G>A	p.Asp268Asn	missense	Exon 8 of 9	NP_057164.3
	GLOD4	NM_001389725.1		c.1000G>A	p.Asp334Asn	missense	Exon 9 of 10	NP_001376654.1
	GLOD4	NM_001389726.1		c.913G>A	p.Asp305Asn	missense	Exon 9 of 10	NP_001376655.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLOD4	ENST00000301329.11	TSL:1 MANE Select	c.802G>A	p.Asp268Asn	missense	Exon 8 of 9	ENSP00000301329.6	Q9HC38-2
	GLOD4	ENST00000301328.9	TSL:1	c.847G>A	p.Asp283Asn	missense	Exon 9 of 10	ENSP00000301328.5	Q9HC38-1
	GLOD4	ENST00000891260.1		c.913G>A	p.Asp305Asn	missense	Exon 9 of 10	ENSP00000561319.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1454438 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724176

African (AFR) AF: 0.00 AC: 0 AN: 33328

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105200

Other (OTH) AF: 0.00 AC: 0 AN: 60146

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	-0.15	T
PhyloP100		7.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.41		Gain of helix (P = 0.0854)
MVP		0.80
MPC		0.58
ClinPred		1.0	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.79

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

Other links and lift over

dbSNP: rs746588800; hg19: chr17-673138;