rs766494478

Variant names:

• chr12-14806619-A-C
• NM_001013698.2:c.62T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-14806619-A-C
• chr12-14806619-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001013698.2(SMCO3):​c.62T>G​(p.Leu21Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMCO3 NM_001013698.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.93

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMCO3	NM_001013698.2	c.62T>G	p.Leu21Arg	missense_variant	Exon 2 of 2	ENST00000316048.2	NP_001013720.2
C12orf60	NM_175874.4	c.-25+2868A>C		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.62T>G	p.Leu21Arg	missense_variant	Exon 2 of 2	1	NM_001013698.2	ENSP00000381895.1
C12orf60	ENST00000330828.3	c.-25+2868A>C		intron_variant	Intron 1 of 1	1	NM_175874.4	ENSP00000331691.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.50		Gain of disorder (P = 0.0138);
MVP		0.45
MPC		0.25
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.87
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-14959553;