dbSNP rs759951731: SCML2:p.Pro268Leu (chrX-18265730-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.803C>T(p.Pro268Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000177 in 1,208,454 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 62 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.00019 ( 0 hom. 60 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.28

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.122168094).

BS2

High Hemizygotes in GnomAd4 at 2 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.803C>T	p.Pro268Leu	missense	Exon 8 of 15	NP_006080.1	Q9UQR0-1
	SCML2	NR_033717.2		n.924C>T		non_coding_transcript_exon	Exon 8 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCML2	ENST00000251900.9	TSL:1 MANE Select	c.803C>T	p.Pro268Leu	missense	Exon 8 of 15	ENSP00000251900.4	Q9UQR0-1
SCML2	ENST00000926833.1		c.803C>T	p.Pro268Leu	missense	Exon 8 of 15	ENSP00000596892.1
SCML2	ENST00000926834.1		c.803C>T	p.Pro268Leu	missense	Exon 9 of 16	ENSP00000596893.1

Frequencies

GnomAD3 genomes

AF:

0.0000809

AC:

AN:

111216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000192

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000115

AC:

AN:

183317

AF XY:

0.0000738

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.000255

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000187

AC:

205

AN:

1097238

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

AN XY:

362634

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26384

American (AMR)

AF:

0.000199

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19376

East Asian (EAS)

AF:

0.00

AC:

AN:

30192

South Asian (SAS)

AF:

0.00

AC:

AN:

54106

European-Finnish (FIN)

AF:

0.0000494

AC:

AN:

40500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.000228

AC:

192

AN:

841280

Other (OTH)

AF:

0.0000651

AC:

AN:

46060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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:

0.0000809

AC:

AN:

111216

Hom.:

Cov.:

AF XY:

0.0000598

AC XY:

AN XY:

33418

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30597

American (AMR)

AF:

0.000192

AC:

AN:

10399

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3541

South Asian (SAS)

AF:

0.00

AC:

AN:

2616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5933

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

53086

Other (OTH)

AF:

0.00

AC:

AN:

1483

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

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:

0.0000522

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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

0.081

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.66

M_CAP

Benign

0.021

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.3

PhyloP100

6.3

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-5.9

REVEL

Benign

0.21

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.011

Polyphen

0.40

Vest4

0.19

MVP

0.21

MPC

0.67

ClinPred

0.41

GERP RS

4.8

Varity_R

0.26

gMVP

0.58

Mutation Taster

=89/11

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