NM_018988.4:c.577G>A

Variant names:

• chr6-13365339-C-T
• rs376523971
• NM_018988.4:c.577G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018988.4(GFOD1):​c.577G>A​(p.Val193Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GFOD1 NM_018988.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.80
• Publications: 5 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12614062).

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.577G>A	p.Val193Ile	missense	Exon 2 of 2	NP_061861.1	Q9NXC2-1
	GFOD1	NM_001242628.2		c.268G>A	p.Val90Ile	missense	Exon 2 of 2	NP_001229557.1	Q9NXC2-2
	GFOD1	NM_001242630.2		c.268G>A	p.Val90Ile	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.577G>A	p.Val193Ile	missense	Exon 2 of 2	ENSP00000368589.3	Q9NXC2-1
	GFOD1	ENST00000379284.1	TSL:2	c.268G>A	p.Val90Ile	missense	Exon 2 of 2	ENSP00000368586.1	Q9NXC2-2
	GFOD1	ENST00000612338.4	TSL:2	c.268G>A	p.Val90Ile	missense	Exon 2 of 2	ENSP00000479493.1	Q9NXC2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.076
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L
PhyloP100		1.8
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.052
Sift	Benign	0.33	T
Sift4G	Benign	0.44	T
Polyphen		0.034	B
Vest4		0.036
MVP		0.28
MPC		0.85
ClinPred		0.16	T
GERP RS		3.5
Varity_R		0.026
gMVP		0.69
Mutation Taster		=99/1	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

dbSNP: rs376523971; hg19: chr6-13365571; COSMIC: COSV64954989;