rs148476450

Variant names:

• chr16-56451734-A-T
• rs148476450
• NM_018233.4:c.122A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018233.4(OGFOD1):​c.122A>T​(p.Glu41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,290 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: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: OGFOD1 NM_018233.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.97
• 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:):

NUDT21 (HGNC:13870): (nudix hydrolase 21) The protein encoded by this gene is one subunit of a cleavage factor required for 3' RNA cleavage and polyadenylation processing. The interaction of the protein with the RNA is one of the earliest steps in the assembly of the 3' end processing complex and facilitates the recruitment of other processing factors. This gene encodes the 25kD subunit of the protein complex, which is composed of four polypeptides. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18275371).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018233.4. 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.122A>T	p.Glu41Val	missense	Exon 1 of 13	NP_060703.3
	OGFOD1	NM_001324357.2		c.122A>T	p.Glu41Val	missense	Exon 1 of 13	NP_001311286.1
	OGFOD1	NM_001324363.2		c.122A>T	p.Glu41Val	missense	Exon 1 of 12	NP_001311292.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGFOD1	ENST00000566157.6	TSL:1 MANE Select	c.122A>T	p.Glu41Val	missense	Exon 1 of 13	ENSP00000457258.1	Q8N543-1
	ENSG00000288725	ENST00000684388.1		n.*1-3745T>A		intron	N/A	ENSP00000507647.1	A0A804HJU2
	OGFOD1	ENST00000924152.1		c.122A>T	p.Glu41Val	missense	Exon 1 of 14	ENSP00000594211.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000718 AC: 18 AN: 250562 AF XY: 0.0000664

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000405

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: 0.000655

GnomAD4 exome AF: 0.0000198 AC: 29 AN: 1461098 Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13 AN XY: 726794

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.000447 AC: 20 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5282

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111906

Other (OTH) AF: 0.000116 AC: 7 AN: 60304

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.000589 AC: 9 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000412 AC: 5

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	0.13
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.0
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.9	D
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.035	D
Polyphen		0.98	D
Vest4		0.28
MVP		0.66
MPC		0.32
ClinPred		0.64	D
GERP RS		5.8
PromoterAI		-0.18	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.41
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs148476450; hg19: chr16-56485646;