dbSNP rs1228987621: SCML2:p.Pro387Arg (chrX-18258157-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006089.3(SCML2):c.1160C>G(p.Pro387Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000165 in 1,209,571 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.30

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29480153).

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.1160C>G	p.Pro387Arg	missense	Exon 10 of 15	NP_006080.1	Q9UQR0-1
	SCML2	NR_033717.2		n.1281C>G		non_coding_transcript_exon	Exon 10 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCML2	ENST00000251900.9	TSL:1 MANE Select	c.1160C>G	p.Pro387Arg	missense	Exon 10 of 15	ENSP00000251900.4	Q9UQR0-1
SCML2	ENST00000926833.1		c.1160C>G	p.Pro387Arg	missense	Exon 10 of 15	ENSP00000596892.1
SCML2	ENST00000926834.1		c.1160C>G	p.Pro387Arg	missense	Exon 11 of 16	ENSP00000596893.1

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111807

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097764

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26390

American (AMR)

AF:

0.00

AC:

AN:

35205

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19384

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841700

Other (OTH)

AF:

0.0000217

AC:

AN:

46075

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

Age Distribution

Exome Het

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:

0.00000894

AC:

AN:

111807

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33969

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30789

American (AMR)

AF:

0.00

AC:

AN:

10593

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3532

South Asian (SAS)

AF:

0.00

AC:

AN:

2658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6093

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53088

Other (OTH)

AF:

0.00

AC:

AN:

1502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000712

Hom.:

Bravo

AF:

0.00000756

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

Pathogenic

0.80

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.17

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

M_CAP

Benign

0.035

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

PhyloP100

6.3

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.29

Sift

Benign

0.84

Sift4G

Benign

0.39

Polyphen

0.83

Vest4

0.35

MutPred

0.50

Gain of sheet (P = 0.0061)

MVP

0.36

MPC

1.1

ClinPred

0.91

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.40

gMVP

0.79

Mutation Taster

=62/38

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