dbSNP rs140760052: SCML2:p.Thr20Ile (chrX-18330619-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006089.3(SCML2):c.59C>T(p.Thr20Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,173,952 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., 9 hem., cov: 23)

Exomes 𝑓: 0.000032 ( 0 hom. 5 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.113

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01360485).

BS2

High Hemizygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006089.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCML2	NM_006089.3	MANE Select	c.59C>T	p.Thr20Ile	missense	Exon 3 of 15	NP_006080.1	Q9UQR0-1
	SCML2	NR_033717.2		n.180C>T		non_coding_transcript_exon	Exon 3 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCML2	ENST00000251900.9	TSL:1 MANE Select	c.59C>T	p.Thr20Ile	missense	Exon 3 of 15	ENSP00000251900.4	Q9UQR0-1
SCML2	ENST00000926833.1		c.59C>T	p.Thr20Ile	missense	Exon 3 of 15	ENSP00000596892.1
SCML2	ENST00000926834.1		c.59C>T	p.Thr20Ile	missense	Exon 4 of 16	ENSP00000596893.1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

111502

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000781

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000572

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

GnomAD2 exomes

AF:

0.000114

AC:

AN:

166061

AF XY:

0.0000186

show subpopulations

Gnomad AFR exome

AF:

0.00122

Gnomad AMR exome

AF:

0.000129

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000131

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000320

AC:

AN:

1062450

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

334680

show subpopulations

African (AFR)

AF:

0.00107

AC:

AN:

25256

American (AMR)

AF:

0.000123

AC:

AN:

32405

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18669

East Asian (EAS)

AF:

0.0000342

AC:

AN:

29279

South Asian (SAS)

AF:

0.00

AC:

AN:

48786

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40127

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4008

European-Non Finnish (NFE)

AF:

0.00000122

AC:

AN:

819221

Other (OTH)

AF:

0.0000224

AC:

AN:

44699

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000269

AC:

AN:

111502

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

AN XY:

33698

show subpopulations

African (AFR)

AF:

0.000781

AC:

AN:

30720

American (AMR)

AF:

0.000572

AC:

AN:

10492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3566

South Asian (SAS)

AF:

0.00

AC:

AN:

2671

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5929

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53068

Other (OTH)

AF:

0.00

AC:

AN:

1490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000311

Hom.:

Bravo

AF:

0.000363

ESP6500AA

AF:

0.00157

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.1

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.42

M_CAP

Benign

0.0016

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

-0.11

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.96

REVEL

Benign

0.063

Sift

Benign

0.36

Sift4G

Benign

0.22

Polyphen

0.013

Vest4

0.086

MVP

0.043

MPC

0.64

ClinPred

0.021

GERP RS

-0.080

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.17

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over