chr12-27488523-C-G

Variant names:

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

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>G​(p.Asp192Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMCO2 NM_001395208.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.14650634).

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>G	p.Asp192Glu	missense	Exon 6 of 9	NP_001382137.1	A6NFE2
	SMCO2	NM_001145010.3		c.576C>G	p.Asp192Glu	missense	Exon 6 of 9	NP_001138482.1	A6NFE2
	SMCO2	NM_001387218.3		c.189C>G	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>G	p.Asp192Glu	missense	Exon 6 of 9	ENSP00000441688.1	A6NFE2
	SMCO2	ENST00000298876.8	TSL:5	c.426C>G	p.Asp142Glu	missense	Exon 5 of 8	ENSP00000298876.4	J3KNC3
	SMCO2	ENST00000698358.1		c.189C>G	p.Asp63Glu	missense	Exon 3 of 6	ENSP00000513681.1	A0A8V8TM60

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.24
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.74
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.11	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	0.060
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)		0.090		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;