6-13365162-C-T

Variant names:

• chr6-13365162-C-T
• NM_018988.4:c.754G>A

Variant summary

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

The NM_018988.4(GFOD1):​c.754G>A​(p.Val252Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GFOD1 NM_018988.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

Genes affected

GFOD1 (HGNC:21096): (Gfo/Idh/MocA-like oxidoreductase domain containing 1) Predicted to enable nucleotide binding activity and oxidoreductase activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFOD1	NM_018988.4	c.754G>A	p.Val252Met	missense_variant	Exon 2 of 2	ENST00000379287.4	NP_061861.1
GFOD1	NM_001242628.2	c.445G>A	p.Val149Met	missense_variant	Exon 2 of 2		NP_001229557.1
GFOD1	NM_001242630.2	c.445G>A	p.Val149Met	missense_variant	Exon 2 of 2		NP_001229559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFOD1	ENST00000379287.4	c.754G>A	p.Val252Met	missense_variant	Exon 2 of 2	1	NM_018988.4	ENSP00000368589.3
GFOD1	ENST00000379284.1	c.445G>A	p.Val149Met	missense_variant	Exon 2 of 2	2		ENSP00000368586.1
GFOD1	ENST00000612338.4	c.445G>A	p.Val149Met	missense_variant	Exon 2 of 2	2		ENSP00000479493.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.754G>A (p.V252M) alteration is located in exon 2 (coding exon 2) of the GFOD1 gene. This alteration results from a G to A substitution at nucleotide position 754, causing the valine (V) at amino acid position 252 to be replaced by a methionine (M). 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	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	.;T;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	.;D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.1	N;N;.
REVEL	Benign	0.21
Sift	Uncertain	0.024	D;D;.
Sift4G	Uncertain	0.030	D;D;D
Polyphen		0.97	.;D;.
Vest4		0.65
MutPred		0.62		.;Gain of loop (P = 0.1069);.;
MVP		0.74
MPC		1.3
ClinPred		0.82	D
GERP RS		5.7
Varity_R		0.27
gMVP		0.88

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: chr6-13365394;