NM_024648.3:c.544C>T

Variant names:

• chr17-82405325-G-A
• rs527568467
• NM_024648.3:c.544C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024648.3(OGFOD3):​c.544C>T​(p.Arg182Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,607,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R182L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: OGFOD3 NM_024648.3 missense, splice_region
• Scores: Splicing: ADA: 0.0008834
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024648.3. 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.544C>T	p.Arg182Trp	missense splice_region	Exon 6 of 9	NP_078924.1	Q6PK18-1
	OGFOD3	NM_175902.5		c.544C>T	p.Arg182Trp	missense splice_region	Exon 6 of 10	NP_787098.3
	OGFOD3	NR_033265.2		n.637C>T		splice_region non_coding_transcript_exon	Exon 6 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGFOD3	ENST00000313056.10	TSL:2 MANE Select	c.544C>T	p.Arg182Trp	missense splice_region	Exon 6 of 9	ENSP00000320116.5	Q6PK18-1
	OGFOD3	ENST00000329197.9	TSL:1	c.544C>T	p.Arg182Trp	missense splice_region	Exon 6 of 10	ENSP00000330075.5	Q6PK18-2
	OGFOD3	ENST00000580445.5	TSL:1	n.*155C>T		splice_region non_coding_transcript_exon	Exon 6 of 10	ENSP00000463566.1	J3QLI8

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151822 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251268 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1455240 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 724128

African (AFR) AF: 0.00 AC: 0 AN: 33328

American (AMR) AF: 0.00 AC: 0 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25956

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39526

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52748

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000452 AC: 5 AN: 1107218

Other (OTH) AF: 0.0000500 AC: 3 AN: 60034

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151942 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74272

African (AFR) AF: 0.00 AC: 0 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.22
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		1.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.53		Gain of catalytic residue at L180 (P = 0.0041)
MVP		0.45
MPC		0.30
ClinPred		0.92	D
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.40
gMVP		0.79
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00088
dbscSNV1_RF	Benign	0.052
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: rs527568467; hg19: chr17-80363201;