NM_000608.4:c.76C>A

Variant names:

• chr9-114329980-C-A
• NM_000608.4:c.76C>A

Variant summary

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

The NM_000608.4(ORM2):​c.76C>A​(p.Leu26Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 19)
• Consequence: ORM2 NM_000608.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.23
• Publications: 0 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]

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=0.051127434).

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.76C>A	p.Leu26Ile	missense	Exon 1 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.76C>A	p.Leu26Ile	missense	Exon 1 of 6	ENSP00000394936.2	P19652
	ORM2	ENST00000893195.1		c.76C>A	p.Leu26Ile	missense	Exon 1 of 7	ENSP00000563254.1
	ORM2	ENST00000893198.1		c.76C>A	p.Leu26Ile	missense	Exon 1 of 6	ENSP00000563257.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 19

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	0.12
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.58
DANN	Benign	0.85
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-2.2
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.057
Sift	Benign	0.38	T
Sift4G	Benign	0.26	T
Polyphen		0.14	B
Vest4		0.14
MutPred		0.32		Gain of catalytic residue at P28 (P = 0.0426)
MVP		0.13
MPC		2.6
ClinPred		0.080	T
GERP RS		-5.5
PromoterAI		0.017	Neutral
Varity_R		0.15
gMVP		0.36
Mutation Taster		=87/13	polymorphism

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

hg19: chr9-117092260;