Variant 12-14806152-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001013698.2(SMCO3):c.529C>T(p.Arg177Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,613,990 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SMCO3
NM_001013698.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.72

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]

SMCO3 links:

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

C12orf60 links:

(HGNC:):

links:

Genome browser will be placed here

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=0.04189664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMCO3	NM_001013698.2 linkuse as main transcript	c.529C>T	p.Arg177Cys	missense_variant	2/2	ENST00000316048.2
C12orf60	NM_175874.4 linkuse as main transcript	c.-25+2401G>A		intron_variant		ENST00000330828.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SMCO3	ENST00000316048.2 linkuse as main transcript	c.529C>T	p.Arg177Cys	missense_variant	2/2	1	NM_001013698.2	P1
C12orf60	ENST00000330828.3 linkuse as main transcript	c.-25+2401G>A		intron_variant		1	NM_175874.4	P1
	ENST00000651868.1 linkuse as main transcript	n.1045G>A		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000441

AC:

AN:

249564

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000445

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000131

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000744

AC:

Asia WGS

AF:

0.00346

AC:

AN:

3478

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 submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.529C>T (p.R177C) alteration is located in exon 2 (coding exon 1) of the SMCO3 gene. This alteration results from a C to T substitution at nucleotide position 529, causing the arginine (R) at amino acid position 177 to be replaced by a cysteine (C). 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

0.18

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.50

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Benign

0.015

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.83

M_CAP

Benign

0.012

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.056

Sift

Benign

0.056

Sift4G

Uncertain

0.019

Polyphen

0.0060

Vest4

0.17

MVP

0.22

MPC

0.033

ClinPred

0.16

GERP RS

3.6

Varity_R

0.14

gMVP

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over