NM_001395208.2:c.721G>C

Variant names:

• chr12-27495743-G-C
• rs752770562
• NM_001395208.2:c.721G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395208.2(SMCO2):​c.721G>C​(p.Asp241His) 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. 16/21 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. D241N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SMCO2 NM_001395208.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05975291).

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.721G>C	p.Asp241His	missense	Exon 8 of 9	NP_001382137.1	A6NFE2
	SMCO2	NM_001145010.3		c.721G>C	p.Asp241His	missense	Exon 8 of 9	NP_001138482.1	A6NFE2
	SMCO2	NM_001387218.3		c.334G>C	p.Asp112His	missense	Exon 5 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.721G>C	p.Asp241His	missense	Exon 8 of 9	ENSP00000441688.1	A6NFE2
	SMCO2	ENST00000298876.8	TSL:5	c.571G>C	p.Asp191His	missense	Exon 7 of 8	ENSP00000298876.4	J3KNC3
	SMCO2	ENST00000698358.1		c.334G>C	p.Asp112His	missense	Exon 5 of 6	ENSP00000513681.1	A0A8V8TM60

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.1
DANN	Benign	0.42
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.23
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.061
Sift	Benign	0.11	T
Sift4G	Benign	0.094	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.13		Gain of helix (P = 0.0199)
MVP		0.014
ClinPred		0.029	T
GERP RS		-2.4
Varity_R		0.045
gMVP		0.048
Mutation Taster		=98/2	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: rs752770562; hg19: chr12-27648676;