16-56462569-C-G

Variant names:

• chr16-56462569-C-G
• rs375464486
• NM_018233.4:c.383C>G

Variant summary

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

The NM_001324362.1(OGFOD1):​c.-38C>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000137 in 1,460,736 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: 0.0000014 (0 hom.)
• Consequence: OGFOD1 NM_001324362.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22
• Publications: 0 publications found

Genes affected

OGFOD1 (HGNC:25585): (2-oxoglutarate and iron dependent oxygenase domain containing 1) Enables peptidyl-proline 3-dioxygenase activity. Involved in several processes, including peptidyl-proline hydroxylation; regulation of translational termination; and stress granule assembly. Located in cytoplasmic stress granule; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288725 (HGNC:):

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=0.34170192).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324362.1. 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
	OGFOD1	NM_018233.4	MANE Select	c.383C>G	p.Ser128Cys	missense	Exon 4 of 13	NP_060703.3
	OGFOD1	NM_001324362.1		c.-38C>G		5_prime_UTR_premature_start_codon_gain	Exon 4 of 13	NP_001311291.1	Q8N543-2
	OGFOD1	NM_001324357.2		c.380C>G	p.Ser127Cys	missense	Exon 4 of 13	NP_001311286.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGFOD1	ENST00000566157.6	TSL:1 MANE Select	c.383C>G	p.Ser128Cys	missense	Exon 4 of 13	ENSP00000457258.1	Q8N543-1
	ENSG00000288725	ENST00000684388.1		n.*1-14580G>C		intron	N/A	ENSP00000507647.1	A0A804HJU2
	OGFOD1	ENST00000924152.1		c.383C>G	p.Ser128Cys	missense	Exon 4 of 14	ENSP00000594211.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460736 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 726792

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111080

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

ClinVar submissions as Germline

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	0.079
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.2
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.3	D
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.040	D
Polyphen		0.57	P
Vest4		0.52
MVP		0.70
MPC		0.33
ClinPred		0.95	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.55

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: rs375464486; hg19: chr16-56496481;