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GeneBe

12-14806090-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001013698.2(SMCO3):c.591G>T(p.Lys197Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.496
Variant links:
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)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.043408275).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMCO3NM_001013698.2 linkuse as main transcriptc.591G>T p.Lys197Asn missense_variant 2/2 ENST00000316048.2
C12orf60NM_175874.4 linkuse as main transcriptc.-25+2339C>A intron_variant ENST00000330828.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMCO3ENST00000316048.2 linkuse as main transcriptc.591G>T p.Lys197Asn missense_variant 2/21 NM_001013698.2 P1
C12orf60ENST00000330828.3 linkuse as main transcriptc.-25+2339C>A intron_variant 1 NM_175874.4 P1
ENST00000651868.1 linkuse as main transcriptn.983C>A 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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 14, 2022The c.591G>T (p.K197N) alteration is located in exon 2 (coding exon 1) of the SMCO3 gene. This alteration results from a G to T substitution at nucleotide position 591, causing the lysine (K) at amino acid position 197 to be replaced by an asparagine (N). 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
Benign
0.11
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
Cadd
Benign
15
Dann
Uncertain
1.0
DEOGEN2
Benign
0.0026
T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.043
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.073
Sift
Uncertain
0.013
D
Sift4G
Benign
0.066
T
Polyphen
0.0
B
Vest4
0.11
MutPred
0.23
Loss of ubiquitination at K197 (P = 0.0071);
MVP
0.048
MPC
0.036
ClinPred
0.48
T
GERP RS
0.53
Varity_R
0.26
gMVP
0.50

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: chr12-14959024; API