12-14806118-A-G

Variant summary

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

The NM_001013698.2(SMCO3):c.563T>C(p.Leu188Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMCO3 NM_001013698.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32

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)

(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/exons	MANE	UniProt
SMCO3	NM_001013698.2	c.563T>C	p.Leu188Pro	missense_variant	2/2	ENST00000316048.2
C12orf60	NM_175874.4	c.-25+2367A>G		intron_variant		ENST00000330828.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMCO3	ENST00000316048.2	c.563T>C	p.Leu188Pro	missense_variant	2/2	1	NM_001013698.2	P1
C12orf60	ENST00000330828.3	c.-25+2367A>G		intron_variant		1	NM_175874.4	P1
	ENST00000651868.1	n.1011A>G		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.563T>C (p.L188P) alteration is located in exon 2 (coding exon 1) of the SMCO3 gene. This alteration results from a T to C substitution at nucleotide position 563, causing the leucine (L) at amino acid position 188 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.57		Gain of loop (P = 3e-04);
MVP		0.20
MPC		0.26
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.97
gMVP		0.97

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: chr12-14959052;