NM_000608.4:c.157G>A

Variant names:

• chr9-114330476-G-A
• rs201562247
• NM_000608.4:c.157G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000608.4(ORM2):​c.157G>A​(p.Glu53Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,610,044 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000080 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: ORM2 NM_000608.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.540
• Publications: 1 publications found

Genes affected

ORM2 (HGNC:8499): (orosomucoid 2) This gene encodes a key acute phase plasma protein. Because of its increase due to acute inflammation, this protein is classified as an acute-phase reactant. The specific function of this protein has not yet been determined; however, it may be involved in aspects of immunosuppression. [provided by RefSeq, Jul 2008]

AKNA (HGNC:24108): (AT-hook transcription factor) Predicted to enable DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in centrosome; cytosol; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.051913857).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000608.4. 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
	ORM2	NM_000608.4	MANE Select	c.157G>A	p.Glu53Lys	missense	Exon 2 of 6	NP_000599.1	P19652

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORM2	ENST00000431067.4	TSL:1 MANE Select	c.157G>A	p.Glu53Lys	missense	Exon 2 of 6	ENSP00000394936.2	P19652
	ORM2	ENST00000893195.1		c.157G>A	p.Glu53Lys	missense	Exon 2 of 7	ENSP00000563254.1
	ORM2	ENST00000893198.1		c.157G>A	p.Glu53Lys	missense	Exon 2 of 6	ENSP00000563257.1

Frequencies

GnomAD3 genomes AF: 0.0000801 AC: 12 AN: 149878 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000760

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000483

GnomAD2 exomes AF: 0.0000917 AC: 23 AN: 250732 AF XY: 0.000103

Gnomad AFR exome AF: 0.000253

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000122 AC: 178 AN: 1460166 Hom.: 1 Cov.: 32 AF XY: 0.000124 AC XY: 90 AN XY: 726500

African (AFR) AF: 0.0000925 AC: 3 AN: 32420

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39696

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86222

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

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

European-Non Finnish (NFE) AF: 0.000145 AC: 161 AN: 1111480

Other (OTH) AF: 0.0000829 AC: 5 AN: 60324

GnomAD4 genome AF: 0.0000801 AC: 12 AN: 149878 Hom.: 0 Cov.: 29 AF XY: 0.0000547 AC XY: 4 AN XY: 73184

African (AFR) AF: 0.0000760 AC: 3 AN: 39480

American (AMR) AF: 0.00 AC: 0 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4784

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

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67928

Other (OTH) AF: 0.000483 AC: 1 AN: 2072

Alfa AF: 0.0000901 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000109

EpiControl AF: 0.000178

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	0.068
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Benign	0.62
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.54
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.022
Sift	Benign	0.13	T
Sift4G	Uncertain	0.040	D
Polyphen		0.40	B
Vest4		0.25
MVP		0.31
MPC		1.9
ClinPred		0.010	T
GERP RS		1.2
Varity_R		0.14
gMVP		0.59
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201562247; hg19: chr9-117092756; COSMIC: COSV52280060; COSMIC: COSV52280060;