17-769911-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/20 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLOD4	NM_016080.4	c.789A>T	p.Glu263Asp	missense_variant	Exon 8 of 9	ENST00000301329.11	NP_057164.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLOD4	ENST00000301329.11	c.789A>T	p.Glu263Asp	missense_variant	Exon 8 of 9	1	NM_016080.4	ENSP00000301329.6

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000361

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.789A>T (p.E263D) alteration is located in exon 8 (coding exon 8) of the GLOD4 gene. This alteration results from a A to T substitution at nucleotide position 789, causing the glutamic acid (E) at amino acid position 263 to be replaced by an aspartic acid (D). 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	0.14
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;D;D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.89	T
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.3	N;.;N
REVEL	Benign	0.095
Sift	Benign	0.12	T;.;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.016	B;.;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-673151;