12-14806259-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013698.2(SMCO3):c.422C>A(p.Thr141Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 4.07

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21233737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMCO3	NM_001013698.2	c.422C>A	p.Thr141Lys	missense_variant	2/2	ENST00000316048.2
C12orf60	NM_175874.4	c.-25+2508G>T		intron_variant		ENST00000330828.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMCO3	ENST00000316048.2	c.422C>A	p.Thr141Lys	missense_variant	2/2	1	NM_001013698.2	P1
C12orf60	ENST00000330828.3	c.-25+2508G>T		intron_variant		1	NM_175874.4	P1
	ENST00000651868.1	n.1152G>T		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

Oct 04, 2022

The c.422C>A (p.T141K) alteration is located in exon 2 (coding exon 1) of the SMCO3 gene. This alteration results from a C to A substitution at nucleotide position 422, causing the threonine (T) at amino acid position 141 to be replaced by a lysine (K). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.0031	T
BayesDel_noAF	Benign	-0.24
Cadd	Uncertain	24
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0060	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.093
Sift	Benign	0.030	D
Sift4G	Benign	0.069	T
Polyphen		0.67	P
Vest4		0.39
MutPred		0.42		Gain of MoRF binding (P = 0.0264);
MVP		0.095
MPC		0.045
ClinPred		0.73	D
GERP RS		4.7
Varity_R		0.39
gMVP		0.87

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: chr12-14959193;