Variant X-18256934-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006089.3(SCML2):c.1370A>G(p.Gln457Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000302 in 1,206,708 control chromosomes in the GnomAD database, including 2 homozygotes. There are 111 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 1 hom., 11 hem., cov: 23)

Exomes 𝑓: 0.00029 ( 1 hom. 100 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88

Variant links:

Genes affected

SCML2 (HGNC:10581): (Scm polycomb group protein like 2) This gene encodes a member of the Polycomb group proteins. These proteins form the Polycomb repressive complexes which are involved in transcriptional repression. The encoded protein binds histone peptides that are monomethylated at lysine residues and may be involved in regulating homeotic gene expression during development. [provided by RefSeq, Jun 2010]

SCML2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0100007355).

BS2

High Hemizygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCML2	NM_006089.3 linkuse as main transcript	c.1370A>G	p.Gln457Arg	missense_variant	11/15	ENST00000251900.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCML2	ENST00000251900.9 linkuse as main transcript	c.1370A>G	p.Gln457Arg	missense_variant	11/15	1	NM_006089.3	P1	Q9UQR0-1
SCML2	ENST00000665583.1 linkuse as main transcript	c.578A>G	p.Gln193Arg	missense_variant	5/8

Frequencies

GnomAD3 genomes

AF:

0.000384

AC:

AN:

111896

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

34062

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00978

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.000225

Gnomad OTH

AF:

0.00199

GnomAD3 exomes

AF:

0.000458

AC:

AN:

179020

Hom.:

AF XY:

0.000675

AC XY:

AN XY:

63750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00784

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000273

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000162

Gnomad OTH exome

AF:

0.00137

GnomAD4 exome

AF:

0.000293

AC:

321

AN:

1094761

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

100

AN XY:

360341

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00983

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000149

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000929

Gnomad4 OTH exome

AF:

0.000675

GnomAD4 genome

AF:

0.000384

AC:

AN:

111947

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

34123

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00978

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000225

Gnomad4 OTH

AF:

0.00197

Alfa

AF:

0.000682

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000412

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

Oct 05, 2021

The c.1370A>G (p.Q457R) alteration is located in exon 11 (coding exon 10) of the SCML2 gene. This alteration results from a A to G substitution at nucleotide position 1370, causing the glutamine (Q) at amino acid position 457 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.029

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.62

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

0.58

Polyphen

0.33

Vest4

0.065

MVP

0.57

MPC

0.97

ClinPred

0.10

GERP RS

5.5

Varity_R

0.21

gMVP

0.65

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