17-771451-T-G

Variant names:

• chr17-771451-T-G
• NM_016080.4:c.417A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016080.4(GLOD4):​c.417A>C​(p.Leu139Phe) 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: 33)
• Consequence: GLOD4 NM_016080.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20816073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLOD4	NM_016080.4	c.417A>C	p.Leu139Phe	missense_variant	Exon 5 of 9	ENST00000301329.11	NP_057164.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLOD4	ENST00000301329.11	c.417A>C	p.Leu139Phe	missense_variant	Exon 5 of 9	1	NM_016080.4	ENSP00000301329.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.417A>C (p.L139F) alteration is located in exon 5 (coding exon 5) of the GLOD4 gene. This alteration results from a A to C substitution at nucleotide position 417, causing the leucine (L) at amino acid position 139 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	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.81
DEOGEN2	Benign	0.026	.;.;T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.90	N;.;N;.
REVEL	Benign	0.016
Sift	Benign	0.70	T;.;T;.
Sift4G	Benign	0.70	T;T;T;T
Polyphen		0.0020	B;.;B;.
Vest4		0.45
MutPred		0.41		.;.;Gain of methylation at K155 (P = 0.0275);.;
MVP		0.58
MPC		0.20
ClinPred		0.58	D
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.060
gMVP		0.28

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: chr17-674691;