Genetic Variant SCML2:p.Ile323Val (chrX-18260273-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006089.3(SCML2):c.967A>G(p.Ile323Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000334 in 1,196,887 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.10

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014018059).

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.967A>G	p.Ile323Val	missense	Exon 9 of 15	NP_006080.1	Q9UQR0-1
	SCML2	NR_033717.2		n.1088A>G		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.967A>G	p.Ile323Val	missense	Exon 9 of 15	ENSP00000251900.4	Q9UQR0-1
SCML2	ENST00000926833.1		c.967A>G	p.Ile323Val	missense	Exon 9 of 15	ENSP00000596892.1
SCML2	ENST00000926834.1		c.967A>G	p.Ile323Val	missense	Exon 10 of 16	ENSP00000596893.1

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111305

Hom.:

Cov.:

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:

0.000560

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:

0.00000575

AC:

AN:

173974

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000767

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000184

AC:

AN:

1085530

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

352800

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26063

American (AMR)

AF:

0.00

AC:

AN:

34127

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19013

East Asian (EAS)

AF:

0.0000333

AC:

AN:

29999

South Asian (SAS)

AF:

0.00

AC:

AN:

51185

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4070

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

835290

Other (OTH)

AF:

0.00

AC:

AN:

45579

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111357

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33603

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30644

American (AMR)

AF:

0.00

AC:

AN:

10391

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.000562

AC:

AN:

3561

South Asian (SAS)

AF:

0.00

AC:

AN:

2608

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53094

Other (OTH)

AF:

0.00

AC:

AN:

1526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000824

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

0.065

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-1.2

CADD

Benign

0.0050

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.019

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.49

M_CAP

Benign

0.0036

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

PhyloP100

-3.1

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.12

REVEL

Benign

0.025

Sift

Benign

0.69

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.020

MVP

0.043

MPC

0.49

ClinPred

0.025

GERP RS

-8.6

Varity_R

0.032

gMVP

0.13

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over