Variant 12-27488512-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001395208.2(SMCO2):c.565C>T(p.Arg189Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,538,666 control chromosomes in the GnomAD database, including 14 homozygotes. 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: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 14 hom. )

Consequence

SMCO2
NM_001395208.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.843

Variant links:

Genes affected

SMCO2 (HGNC:34448): (single-pass membrane protein with coiled-coil domains 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMCO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMCO2	NM_001395208.2 linkuse as main transcript	c.565C>T	p.Arg189Trp	missense_variant	6/9	ENST00000535986.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SMCO2	ENST00000535986.2 linkuse as main transcript	c.565C>T	p.Arg189Trp	missense_variant	6/9	5	NM_001395208.2
SMCO2	ENST00000298876.8 linkuse as main transcript	c.415C>T	p.Arg139Trp	missense_variant	5/8	5		P1
SMCO2	ENST00000698358.1 linkuse as main transcript	c.178C>T	p.Arg60Trp	missense_variant	3/6
SMCO2	ENST00000538647.1 linkuse as main transcript	n.169-7168C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

246

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00132

AC:

195

AN:

147722

Hom.:

AF XY:

0.00125

AC XY:

AN XY:

78294

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.000858

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000480

Gnomad FIN exome

AF:

0.000312

Gnomad NFE exome

AF:

0.00281

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00294

AC:

4076

AN:

1386496

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

1972

AN XY:

683116

show subpopulations

Gnomad4 AFR exome

AF:

0.000675

Gnomad4 AMR exome

AF:

0.000761

Gnomad4 ASJ exome

AF:

0.0000400

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000106

Gnomad4 FIN exome

AF:

0.000448

Gnomad4 NFE exome

AF:

0.00362

Gnomad4 OTH exome

AF:

0.00195

GnomAD4 genome

AF:

0.00162

AC:

246

AN:

152170

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00161

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00283

AC:

ExAC

AF:

0.000774

AC:

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

Jul 20, 2021

The c.565C>T (p.R189W) alteration is located in exon 6 (coding exon 5) of the SMCO2 gene. This alteration results from a C to T substitution at nucleotide position 565, causing the arginine (R) at amino acid position 189 to be replaced by a tryptophan (W). 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

0.13

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.074

T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.48

T;T;.

M_CAP

Benign

0.0028

MetaRNN

Benign

0.0069

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.4

N;D;D

REVEL

Benign

0.022

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.012

D;D;D

Polyphen

0.0

.;B;B

Vest4

0.11

MVP

0.088

ClinPred

0.044

GERP RS

-0.20

Varity_R

0.097

gMVP

0.031

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.26

Position offset: 35

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