12-14806023-C-T

Variant names:

• chr12-14806023-C-T
• rs749737279
• NM_001013698.2:c.658G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001013698.2(SMCO3):​c.658G>A​(p.Val220Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SMCO3 NM_001013698.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32

Genes affected

SMCO3 (HGNC:34401): (single-pass membrane protein with coiled-coil domains 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C12orf60 (HGNC:28726): (chromosome 12 open reading frame 60)

ENSG00000286107 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMCO3	NM_001013698.2	c.658G>A	p.Val220Met	missense_variant	Exon 2 of 2	ENST00000316048.2	NP_001013720.2
C12orf60	NM_175874.4	c.-25+2272C>T		intron_variant	Intron 1 of 1	ENST00000330828.3	NP_787070.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMCO3	ENST00000316048.2	c.658G>A	p.Val220Met	missense_variant	Exon 2 of 2	1	NM_001013698.2	ENSP00000381895.1
C12orf60	ENST00000330828.3	c.-25+2272C>T		intron_variant	Intron 1 of 1	1	NM_175874.4	ENSP00000331691.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457876 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724918

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0026	T
Eigen	Benign	0.020
Eigen_PC	Benign	-0.038
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.10
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.015	D
Polyphen		0.94	P
Vest4		0.60
MutPred		0.26		Loss of methylation at K221 (P = 0.0153);
MVP		0.048
MPC		0.15
ClinPred		0.68	D
GERP RS		3.4
Varity_R		0.13
gMVP		0.94

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

Publications

LitVar

Other links and lift over

dbSNP: rs749737279; hg19: chr12-14958957;