Variant 12-27502066-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001395208.2(SMCO2):c.977G>A(p.Arg326Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000453 in 1,546,024 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

SMCO2
NM_001395208.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMCO2	NM_001395208.2 linkuse as main transcript	c.977G>A	p.Arg326Gln	missense_variant	9/9	ENST00000535986.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SMCO2	ENST00000535986.2 linkuse as main transcript	c.977G>A	p.Arg326Gln	missense_variant	9/9	5	NM_001395208.2
SMCO2	ENST00000298876.8 linkuse as main transcript	c.827G>A	p.Arg276Gln	missense_variant	8/8	5		P1
SMCO2	ENST00000698358.1 linkuse as main transcript	c.590G>A	p.Arg197Gln	missense_variant	6/6
SMCO2	ENST00000541168.1 linkuse as main transcript	n.841G>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.00000665

AC:

AN:

150304

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000430

AC:

AN:

1395720

Hom.:

Cov.:

AF XY:

0.00000436

AC XY:

AN XY:

688350

show subpopulations

Gnomad4 AFR exome

AF:

0.0000323

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000399

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000665

AC:

AN:

150304

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73416

show subpopulations

Gnomad4 AFR

AF:

0.0000250

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Jan 29, 2024

The c.977G>A (p.R326Q) alteration is located in exon 9 (coding exon 8) of the SMCO2 gene. This alteration results from a G to A substitution at nucleotide position 977, causing the arginine (R) at amino acid position 326 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.25

Cadd

Benign

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.13

T;T;T

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.64

T;T;.

M_CAP

Benign

0.0042

MetaRNN

Uncertain

0.66

D;D;D

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.017

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.67

MutPred

0.44

.;Gain of catalytic residue at T321 (P = 3e-04);Gain of catalytic residue at T321 (P = 3e-04);

MVP

0.055

ClinPred

0.78

GERP RS

3.4

Varity_R

0.10

gMVP

0.49

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