6-13365128-G-A

Variant names:

• chr6-13365128-G-A
• NM_018988.4:c.788C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018988.4(GFOD1):​c.788C>T​(p.Thr263Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GFOD1 NM_018988.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.89
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2891553).

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.788C>T	p.Thr263Ile	missense	Exon 2 of 2	NP_061861.1	Q9NXC2-1
	GFOD1	NM_001242628.2		c.479C>T	p.Thr160Ile	missense	Exon 2 of 2	NP_001229557.1	Q9NXC2-2
	GFOD1	NM_001242630.2		c.479C>T	p.Thr160Ile	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.788C>T	p.Thr263Ile	missense	Exon 2 of 2	ENSP00000368589.3	Q9NXC2-1
	GFOD1	ENST00000379284.1	TSL:2	c.479C>T	p.Thr160Ile	missense	Exon 2 of 2	ENSP00000368586.1	Q9NXC2-2
	GFOD1	ENST00000612338.4	TSL:2	c.479C>T	p.Thr160Ile	missense	Exon 2 of 2	ENSP00000479493.1	Q9NXC2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460738 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726710

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111796

Other (OTH) AF: 0.00 AC: 0 AN: 60376

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	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.9
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.068
Sift	Benign	0.034	D
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.50		Loss of catalytic residue at T263 (P = 0.027)
MVP		0.65
MPC		1.1
ClinPred		0.74	D
GERP RS		5.7
Varity_R		0.12
gMVP		0.86
Mutation Taster		=67/33	polymorphism

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: chr6-13365360; COSMIC: COSV101015260;