17-82394400-G-T

Position:

• chr17-82394400-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000329197.9(OGFOD3):​c.967C>A​(p.Leu323Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: OGFOD3 ENST00000329197.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.879

Genes affected

OGFOD3 (HGNC:26174): (2-oxoglutarate and iron dependent oxygenase domain containing 3) Predicted to enable several functions, including L-ascorbic acid binding activity; dioxygenase activity; and iron ion binding activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10905385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGFOD3	NM_024648.3	c.824-1866C>A		intron_variant		ENST00000313056.10	NP_078924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGFOD3	ENST00000313056.10	c.824-1866C>A		intron_variant		2	NM_024648.3	ENSP00000320116	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1455744 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 724012

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000361

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.967C>A (p.L323M) alteration is located in exon 9 (coding exon 9) of the OGFOD3 gene. This alteration results from a C to A substitution at nucleotide position 967, causing the leucine (L) at amino acid position 323 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
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.53
DANN	Benign	0.62
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.052
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.23	T
Polyphen		0.95	P
Vest4		0.23
MutPred		0.16		Gain of helix (P = 0.132);
MVP		0.18
MPC		0.041
ClinPred		0.33	T
GERP RS		-0.49
gMVP		0.19

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: chr17-80352276;