17-770474-C-G

Variant names:

• chr17-770474-C-G
• NM_016080.4:c.577G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016080.4(GLOD4):​c.577G>C​(p.Val193Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: GLOD4 NM_016080.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63

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=0.31391597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLOD4	NM_016080.4	c.577G>C	p.Val193Leu	missense_variant	Exon 6 of 9	ENST00000301329.11	NP_057164.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLOD4	ENST00000301329.11	c.577G>C	p.Val193Leu	missense_variant	Exon 6 of 9	1	NM_016080.4	ENSP00000301329.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.577G>C (p.V193L) alteration is located in exon 6 (coding exon 6) of the GLOD4 gene. This alteration results from a G to C substitution at nucleotide position 577, causing the valine (V) at amino acid position 193 to be replaced by a leucine (L). 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	0.29
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.85
DEOGEN2	Benign	0.028	.;.;T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.6	N;.;N;.
REVEL	Benign	0.12
Sift	Benign	0.39	T;.;T;.
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.31	B;.;B;.
Vest4		0.58
MutPred		0.47		.;.;Loss of sheet (P = 0.0315);.;
MVP		0.72
MPC		0.18
ClinPred		0.60	D
GERP RS		3.8
Varity_R		0.10
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr17-673714;