17-769898-C-G

Variant names:

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

Variant summary

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

The NM_016080.4(GLOD4):​c.802G>C​(p.Asp268His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,454,438 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000076 (0 hom.)
• 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>C	p.Asp268His	missense	Exon 8 of 9	NP_057164.3
	GLOD4	NM_001389725.1		c.1000G>C	p.Asp334His	missense	Exon 9 of 10	NP_001376654.1
	GLOD4	NM_001389726.1		c.913G>C	p.Asp305His	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>C	p.Asp268His	missense	Exon 8 of 9	ENSP00000301329.6	Q9HC38-2
	GLOD4	ENST00000301328.9	TSL:1	c.847G>C	p.Asp283His	missense	Exon 9 of 10	ENSP00000301328.5	Q9HC38-1
	GLOD4	ENST00000891260.1		c.913G>C	p.Asp305His	missense	Exon 9 of 10	ENSP00000561319.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000278 AC: 7 AN: 251474 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000756 AC: 11 AN: 1454438 Hom.: 0 Cov.: 29 AF XY: 0.00000967 AC XY: 7 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: 0.000169 AC: 9 AN: 53410

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

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105200

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

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	-0.045	T
PhyloP100		7.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.46		Gain of catalytic residue at K281 (P = 0.1268)
MVP		0.83
MPC		0.64
ClinPred		0.97	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.81
gMVP		0.85

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;