rs890995265

Variant names:

• chr12-27488523-C-A
• rs890995265
• NM_001395208.2:c.576C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-27488523-C-A
• chr12-27488523-C-G
• chr12-27488523-C-T

Variant summary

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

The NM_001395208.2(SMCO2):​c.576C>A​(p.Asp192Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,387,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: SMCO2 NM_001395208.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601
• Publications: 0 publications found

Genes affected

SMCO2 (HGNC:34448): (single-pass membrane protein with coiled-coil domains 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.14644775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395208.2. 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
	SMCO2	NM_001395208.2	MANE Select	c.576C>A	p.Asp192Glu	missense	Exon 6 of 9	NP_001382137.1	A6NFE2
	SMCO2	NM_001145010.3		c.576C>A	p.Asp192Glu	missense	Exon 6 of 9	NP_001138482.1	A6NFE2
	SMCO2	NM_001387218.3		c.189C>A	p.Asp63Glu	missense	Exon 3 of 6	NP_001374147.1	A0A8V8TM60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMCO2	ENST00000535986.2	TSL:5 MANE Select	c.576C>A	p.Asp192Glu	missense	Exon 6 of 9	ENSP00000441688.1	A6NFE2
	SMCO2	ENST00000298876.8	TSL:5	c.426C>A	p.Asp142Glu	missense	Exon 5 of 8	ENSP00000298876.4	J3KNC3
	SMCO2	ENST00000698358.1		c.189C>A	p.Asp63Glu	missense	Exon 3 of 6	ENSP00000513681.1	A0A8V8TM60

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1387690 Hom.: 0 Cov.: 30 AF XY: 0.00000293 AC XY: 2 AN XY: 683756

African (AFR) AF: 0.00 AC: 0 AN: 31204

American (AMR) AF: 0.00 AC: 0 AN: 34256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25054

East Asian (EAS) AF: 0.00 AC: 0 AN: 35168

South Asian (SAS) AF: 0.00 AC: 0 AN: 75890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49158

Middle Eastern (MID) AF: 0.000352 AC: 2 AN: 5678

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1073734

Other (OTH) AF: 0.00 AC: 0 AN: 57548

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.75
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.60
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.055
Sift	Uncertain	0.015	D
Sift4G	Benign	0.18	T
Polyphen		0.97	D
Vest4		0.071
MutPred		0.36		Gain of catalytic residue at G196 (P = 8e-04)
MVP		0.030
ClinPred		0.43	T
GERP RS		2.4
Varity_R		0.065
gMVP		0.011
Mutation Taster		=97/3	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: rs890995265; hg19: chr12-27641456;