12-27488523-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001395208.2(SMCO2):​c.576C>T​(p.Asp192Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,387,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SMCO2 NM_001395208.2 synonymous
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=0.601 with no splicing effect.

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>T	p.Asp192Asp	synonymous	Exon 6 of 9	NP_001382137.1	A6NFE2
	SMCO2	NM_001145010.3		c.576C>T	p.Asp192Asp	synonymous	Exon 6 of 9	NP_001138482.1	A6NFE2
	SMCO2	NM_001387218.3		c.189C>T	p.Asp63Asp	synonymous	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>T	p.Asp192Asp	synonymous	Exon 6 of 9	ENSP00000441688.1	A6NFE2
	SMCO2	ENST00000298876.8	TSL:5	c.426C>T	p.Asp142Asp	synonymous	Exon 5 of 8	ENSP00000298876.4	J3KNC3
	SMCO2	ENST00000698358.1		c.189C>T	p.Asp63Asp	synonymous	Exon 3 of 6	ENSP00000513681.1	A0A8V8TM60

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000675 AC: 1 AN: 148208 AF XY: 0.0000127

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1387694 Hom.: 0 Cov.: 30 AF XY: 0.00000292 AC XY: 2 AN XY: 683760

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: 0.0000132 AC: 1 AN: 75892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073734

Other (OTH) AF: 0.0000174 AC: 1 AN: 57548

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.95
DANN	Benign	0.56
PhyloP100		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;