rs3182041

Variant names:

• chr9-114325121-A-C
• rs3182041
• NM_000607.4:c.509A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-114325121-A-C
• chr9-114325121-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000607.4(ORM1):​c.509A>C​(p.Lys170Thr) 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. 14/20 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ORM1 NM_000607.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• Publications: 5 publications found

Genes affected

ORM1 (HGNC:8498): (orosomucoid 1) 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08512962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORM1	NM_000607.4	c.509A>C	p.Lys170Thr	missense_variant	Exon 5 of 6	ENST00000259396.9	NP_000598.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORM1	ENST00000259396.9	c.509A>C	p.Lys170Thr	missense_variant	Exon 5 of 6	1	NM_000607.4	ENSP00000259396.8
ORM1	ENST00000477456.1	n.292A>C		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461498 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727052

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44704

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111738

Other (OTH) AF: 0.00 AC: 0 AN: 60366

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.87
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.049	N
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.34
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.081
Sift	Benign	0.20	T
Sift4G	Uncertain	0.027	D
Vest4		0.23
MutPred		0.50		Loss of methylation at K170 (P = 0.0049);
MVP		0.076
MPC		0.24
ClinPred		0.024	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.23
Mutation Taster		=93/7	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: rs3182041; hg19: chr9-117087401;