9-114329998-A-T

Variant names:

• chr9-114329998-A-T
• rs755434660
• NM_000608.4:c.94A>T

Variant summary

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

The NM_000608.4(ORM2):​c.94A>T​(p.Thr32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T32A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ORM2 NM_000608.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• 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: 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=0.30898657).

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.94A>T	p.Thr32Ser	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.94A>T	p.Thr32Ser	missense	Exon 1 of 6	ENSP00000394936.2	P19652
	ORM2	ENST00000893195.1		c.94A>T	p.Thr32Ser	missense	Exon 1 of 7	ENSP00000563254.1
	ORM2	ENST00000893198.1		c.94A>T	p.Thr32Ser	missense	Exon 1 of 6	ENSP00000563257.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD2 exomes AF: 0.00000475 AC: 1 AN: 210330 AF XY: 0.00000879

Gnomad AFR exome AF: 0.00

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: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440610 Hom.: 0 Cov.: 28 AF XY: 0.00000140 AC XY: 1 AN XY: 715136

African (AFR) AF: 0.00 AC: 0 AN: 31482

American (AMR) AF: 0.00 AC: 0 AN: 42440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 39166

South Asian (SAS) AF: 0.00 AC: 0 AN: 84542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1099376

Other (OTH) AF: 0.00 AC: 0 AN: 59392

GnomAD4 genome Cov.: 20

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	23
DANN	Benign	0.89
DEOGEN2	Benign	0.082	T
Eigen	Benign	0.093
Eigen_PC	Benign	-0.066
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.5
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.066
Sift	Benign	0.13	T
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.17
MutPred		0.51		Gain of glycosylation at T32 (P = 0.1053)
MVP		0.36
MPC		1.4
ClinPred		0.23	T
GERP RS		2.8
PromoterAI		-0.019	Neutral
Varity_R		0.25
gMVP		0.29
Mutation Taster		=84/16	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

dbSNP: rs755434660; hg19: chr9-117092278;