NM_016080.4:c.789A>T

Variant names:

• chr17-769911-T-A
• NM_016080.4:c.789A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016080.4(GLOD4):​c.789A>T​(p.Glu263Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,459,122 control chromosomes in the GnomAD database, including 1 homozygotes. 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)
  • Exomes 𝑓: 0.0000082 (1 hom.)
• Consequence: GLOD4 NM_016080.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0670
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26975143).

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.789A>T	p.Glu263Asp	missense	Exon 8 of 9	NP_057164.3
	GLOD4	NM_001389725.1		c.987A>T	p.Glu329Asp	missense	Exon 9 of 10	NP_001376654.1
	GLOD4	NM_001389726.1		c.900A>T	p.Glu300Asp	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.789A>T	p.Glu263Asp	missense	Exon 8 of 9	ENSP00000301329.6	Q9HC38-2
	GLOD4	ENST00000301328.9	TSL:1	c.834A>T	p.Glu278Asp	missense	Exon 9 of 10	ENSP00000301328.5	Q9HC38-1
	GLOD4	ENST00000891260.1		c.900A>T	p.Glu300Asp	missense	Exon 9 of 10	ENSP00000561319.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1459122 Hom.: 1 Cov.: 29 AF XY: 0.0000110 AC XY: 8 AN XY: 726104

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1109516

Other (OTH) AF: 0.00 AC: 0 AN: 60286

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.086
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.89	T
PhyloP100		-0.067
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.095
Sift	Benign	0.12	T
Sift4G	Benign	0.19	T
Polyphen		0.016	B
Vest4		0.31
MutPred		0.29		Loss of helix (P = 0.079)
MVP		0.73
MPC		0.12
ClinPred		0.92	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.44
Mutation Taster		=82/18	polymorphism

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

hg19: chr17-673151;