6-13365162-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018988.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFOD1	NM_018988.4	MANE Select	c.754G>A	p.Val252Met	missense	Exon 2 of 2	NP_061861.1	Q9NXC2-1
	GFOD1	NM_001242628.2		c.445G>A	p.Val149Met	missense	Exon 2 of 2	NP_001229557.1	Q9NXC2-2
	GFOD1	NM_001242630.2		c.445G>A	p.Val149Met	missense	Exon 2 of 2	NP_001229559.1	Q9NXC2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFOD1	ENST00000379287.4	TSL:1 MANE Select	c.754G>A	p.Val252Met	missense	Exon 2 of 2	ENSP00000368589.3	Q9NXC2-1
	GFOD1	ENST00000379284.1	TSL:2	c.445G>A	p.Val149Met	missense	Exon 2 of 2	ENSP00000368586.1	Q9NXC2-2
	GFOD1	ENST00000612338.4	TSL:2	c.445G>A	p.Val149Met	missense	Exon 2 of 2	ENSP00000479493.1	Q9NXC2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.21
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.030	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
Mutation Taster		=32/68	disease causing

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

Other links and lift over

hg19: chr6-13365394;