rs371136180

Variant names:

• chr16-56453280-A-C
• rs371136180
• NM_018233.4:c.172A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-56453280-A-C
• chr16-56453280-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001324359.1(OGFOD1):​c.-155A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,824 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: 6.8e-7 (0 hom.)
• Consequence: OGFOD1 NM_001324359.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.790
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06231612).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324359.1. 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.172A>C	p.Met58Leu	missense	Exon 2 of 13	NP_060703.3
	OGFOD1	NM_001324359.1		c.-155A>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 13	NP_001311288.1
	OGFOD1	NM_001324360.2		c.-155A>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 13	NP_001311289.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGFOD1	ENST00000566157.6	TSL:1 MANE Select	c.172A>C	p.Met58Leu	missense	Exon 2 of 13	ENSP00000457258.1	Q8N543-1
	ENSG00000288725	ENST00000684388.1		n.*1-5291T>G		intron	N/A	ENSP00000507647.1	A0A804HJU2
	OGFOD1	ENST00000924152.1		c.172A>C	p.Met58Leu	missense	Exon 2 of 14	ENSP00000594211.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250330 AF XY: 0.00

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460824 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726668

African (AFR) AF: 0.0000300 AC: 1 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 85994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111762

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

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	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.83
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.79
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.76	N
Sift	Benign	0.18	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.37		Loss of sheet (P = 0.302)
MVP		0.32
MPC		0.11
ClinPred		0.036	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.053
gMVP		0.34

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: rs371136180; hg19: chr16-56487192;