NM_018988.4:c.701C>G

Variant names:

• chr6-13365215-G-C
• rs776888360
• NM_018988.4:c.701C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018988.4(GFOD1):​c.701C>G​(p.Thr234Ser) 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: 10.0
• 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.701C>G	p.Thr234Ser	missense	Exon 2 of 2	NP_061861.1	Q9NXC2-1
	GFOD1	NM_001242628.2		c.392C>G	p.Thr131Ser	missense	Exon 2 of 2	NP_001229557.1	Q9NXC2-2
	GFOD1	NM_001242630.2		c.392C>G	p.Thr131Ser	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.701C>G	p.Thr234Ser	missense	Exon 2 of 2	ENSP00000368589.3	Q9NXC2-1
	GFOD1	ENST00000379284.1	TSL:2	c.392C>G	p.Thr131Ser	missense	Exon 2 of 2	ENSP00000368586.1	Q9NXC2-2
	GFOD1	ENST00000612338.4	TSL:2	c.392C>G	p.Thr131Ser	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	Benign	0.20
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.58
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		10
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.30
Sift	Benign	0.066	T
Sift4G	Benign	0.086	T
Polyphen		0.79	P
Vest4		0.47
MutPred		0.83		Gain of sheet (P = 0.0827)
MVP		0.74
MPC		1.5
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.29
gMVP		0.87
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

dbSNP: rs776888360; hg19: chr6-13365447;