17-775892-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016080.4(GLOD4):​c.289G>T​(p.Val97Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GLOD4
NM_016080.4 missense

Scores

2
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.3211106).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GLOD4NM_016080.4 linkc.289G>T p.Val97Phe missense_variant Exon 4 of 9 ENST00000301329.11 NP_057164.3 Q9HC38-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GLOD4ENST00000301329.11 linkc.289G>T p.Val97Phe missense_variant Exon 4 of 9 1 NM_016080.4 ENSP00000301329.6 Q9HC38-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461228
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
727020
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.289G>T (p.V97F) alteration is located in exon 4 (coding exon 4) of the GLOD4 gene. This alteration results from a G to T substitution at nucleotide position 289, causing the valine (V) at amino acid position 97 to be replaced by a phenylalanine (F). 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
0.25
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.035
.;.;T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.037
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.32
T;T;T;T
MetaSVM
Benign
-0.85
T
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.2
N;.;N;.
REVEL
Benign
0.21
Sift
Benign
0.34
T;.;T;.
Sift4G
Benign
0.22
T;T;T;T
Polyphen
0.036
B;.;B;.
Vest4
0.67
MutPred
0.42
.;.;Gain of loop (P = 0.0851);.;
MVP
0.62
MPC
0.18
ClinPred
0.98
D
GERP RS
5.0
Varity_R
0.54
gMVP
0.74

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: chr17-679132; COSMIC: COSV100022391; COSMIC: COSV100022391; API