X-18246675-C-T

Position:

chrX-18246675-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006089.3(SCML2):c.1724G>A(p.Arg575Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000048 in 1,208,576 control chromosomes in the GnomAD database, including 1 homozygotes. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000052 ( 1 hom. 16 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.283

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:

SCML2 (HGNC:):

SCML2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03892407).

BP6

Variant X-18246675-C-T is Benign according to our data. Variant chrX-18246675-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2520012.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCML2	NM_006089.3 linkuse as main transcript	c.1724G>A	p.Arg575Gln	missense_variant	13/15	ENST00000251900.9	NP_006080.1	Q9UQR0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCML2	ENST00000251900.9 linkuse as main transcript	c.1724G>A	p.Arg575Gln	missense_variant	13/15	1	NM_006089.3	ENSP00000251900.4	Q9UQR0-1
SCML2	ENST00000398048.4 linkuse as main transcript	c.38G>A	p.Arg13Gln	missense_variant	1/4	1		ENSP00000381126.4	Q9UQR0-2
SCML2	ENST00000665583.1 linkuse as main transcript	c.932G>A	p.Arg311Gln	missense_variant	7/8			ENSP00000499630.1	B4DRC2
SCML2	ENST00000420857.6 linkuse as main transcript	c.266G>A	p.Arg89Gln	missense_variant	2/3	2		ENSP00000407315.2	H0Y6S1

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111622

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33822

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000282

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

GnomAD3 exomes

AF:

0.0000709

AC:

AN:

183311

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

67771

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000216

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1096954

Hom.:

Cov.:

AF XY:

0.0000442

AC XY:

AN XY:

362328

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00136

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000476

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111622

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33822

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.64

DANN

Benign

0.15

DEOGEN2

Benign

0.023

T;.

FATHMM_MKL

Benign

0.00091

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

N;.

PrimateAI

Benign

0.18

PROVEAN

Benign

0.22

N;.

REVEL

Benign

0.070

Sift

Benign

0.42

T;.

Sift4G

Benign

0.65

T;T

Polyphen

0.010

B;.

Vest4

0.041

MutPred

0.24

Gain of glycosylation at S576 (P = 0.0869);.;

MVP

0.068

MPC

0.68

ClinPred

0.015

GERP RS

0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.033

gMVP

0.24

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