Genetic Variant SCML2:p.Ser333Leu (chrX-18260242-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006089.3(SCML2):c.998C>T(p.Ser333Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,091,438 control chromosomes in the GnomAD database, including 1 homozygotes. There are 11 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: not found (cov: 22)

Exomes 𝑓: 0.000024 ( 1 hom. 11 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0310

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.079657406).

BS2

High Hemizygotes in GnomAdExome4 at 11 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.998C>T	p.Ser333Leu	missense	Exon 9 of 15	NP_006080.1	Q9UQR0-1
	SCML2	NR_033717.2		n.1119C>T		non_coding_transcript_exon	Exon 9 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCML2	ENST00000251900.9	TSL:1 MANE Select	c.998C>T	p.Ser333Leu	missense	Exon 9 of 15	ENSP00000251900.4	Q9UQR0-1
SCML2	ENST00000926833.1		c.998C>T	p.Ser333Leu	missense	Exon 9 of 15	ENSP00000596892.1
SCML2	ENST00000926834.1		c.998C>T	p.Ser333Leu	missense	Exon 10 of 16	ENSP00000596893.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000278

AC:

AN:

179921

AF XY:

0.0000310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000148

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000371

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000238

AC:

AN:

1091438

Hom.:

Cov.:

AF XY:

0.0000308

AC XY:

AN XY:

357526

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26262

American (AMR)

AF:

0.00

AC:

AN:

35004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19253

East Asian (EAS)

AF:

0.0000332

AC:

AN:

30110

South Asian (SAS)

AF:

0.00

AC:

AN:

53068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4113

European-Non Finnish (NFE)

AF:

0.0000299

AC:

AN:

837425

Other (OTH)

AF:

0.00

AC:

AN:

45823

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

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

0.083

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.92

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.29

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.59

M_CAP

Benign

0.0087

MetaRNN

Benign

0.080

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.031

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.012

Sift

Benign

0.031

Sift4G

Benign

0.32

Polyphen

0.0010

Vest4

0.068

MutPred

0.31

Loss of disorder (P = 0.0347)

MVP

0.043

MPC

0.52

ClinPred

0.031

GERP RS

-1.7

Varity_R

0.081

gMVP

0.28

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over