rs762265516

Variant names:

• chr9-114330492-C-G
• NM_000608.4:c.173C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-114330492-C-G
• chr9-114330492-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000608.4(ORM2):​c.173C>G​(p.Ser58Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ORM2 NM_000608.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.16

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23434097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORM2	NM_000608.4	c.173C>G	p.Ser58Trp	missense_variant	Exon 2 of 6	ENST00000431067.4	NP_000599.1
AKNA	XR_929844.4	n.*12G>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORM2	ENST00000431067.4	c.173C>G	p.Ser58Trp	missense_variant	Exon 2 of 6	1	NM_000608.4	ENSP00000394936.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460818 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726790

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.0090
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.8	L
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.089
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.31
MutPred		0.44		Loss of disorder (P = 8e-04);
MVP		0.34
MPC		2.8
ClinPred		0.94	D
GERP RS		-6.2
Varity_R		0.30
gMVP		0.51

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-117092772;