17-82394483-C-A

Variant names:

• chr17-82394483-C-A
• ENST00000329197.9:c.884G>T

Variant summary

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

The NM_175902.5(OGFOD3):​c.884G>T​(p.Ser295Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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 NM_175902.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.273
• Publications: 0 publications found

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

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=0.08637771).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175902.5. 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
	OGFOD3	NM_024648.3	MANE Select	c.824-1949G>T		intron	N/A	NP_078924.1	Q6PK18-1
	OGFOD3	NM_175902.5		c.884G>T	p.Ser295Ile	missense	Exon 9 of 10	NP_787098.3
	OGFOD3	NR_033265.2		n.977G>T		non_coding_transcript_exon	Exon 9 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGFOD3	ENST00000329197.9	TSL:1	c.884G>T	p.Ser295Ile	missense	Exon 9 of 10	ENSP00000330075.5	Q6PK18-2
	OGFOD3	ENST00000313056.10	TSL:2 MANE Select	c.824-1949G>T		intron	N/A	ENSP00000320116.5	Q6PK18-1
	OGFOD3	ENST00000580445.5	TSL:1	n.*495G>T		non_coding_transcript_exon	Exon 9 of 10	ENSP00000463566.1	J3QLI8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461734 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727166

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

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

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

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	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.8
DANN	Benign	0.94
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.27
PROVEAN	Benign	0.98	N
REVEL	Benign	0.031
Sift	Benign	0.059	T
Sift4G	Benign	0.064	T
Polyphen		0.75	P
Vest4		0.14
MutPred		0.17		Gain of helix (P = 0.0034)
MVP		0.14
MPC		0.18
ClinPred		0.84	D
GERP RS		0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.67

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: chr17-80352359; COSMIC: COSV57343173; COSMIC: COSV57343173;