Genetic Variant NM_006089.3:c.2020A>G (chrX-18241334-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006089.3(SCML2):c.2020A>G(p.Met674Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000335 in 1,195,631 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 2 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: 7.51

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 -4 ACMG points.

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.2020A>G	p.Met674Val	missense	Exon 15 of 15	NP_006080.1	Q9UQR0-1
	SCML2	NR_033717.2		n.2141A>G		non_coding_transcript_exon	Exon 15 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCML2	ENST00000251900.9	TSL:1 MANE Select	c.2020A>G	p.Met674Val	missense	Exon 15 of 15	ENSP00000251900.4	Q9UQR0-1
SCML2	ENST00000398048.4	TSL:1	c.334A>G	p.Met112Val	missense	Exon 3 of 4	ENSP00000381126.4	Q9UQR0-2
SCML2	ENST00000926833.1		c.2020A>G	p.Met674Val	missense	Exon 15 of 15	ENSP00000596892.1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000958

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:

0.000672

GnomAD4 exome

AF:

0.00000185

AC:

AN:

1083871

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

350669

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26139

American (AMR)

AF:

0.00

AC:

AN:

34108

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19071

East Asian (EAS)

AF:

0.00

AC:

AN:

29979

South Asian (SAS)

AF:

0.00

AC:

AN:

51638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40183

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4103

European-Non Finnish (NFE)

AF:

0.00000240

AC:

AN:

833172

Other (OTH)

AF:

0.00

AC:

AN:

45478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111760

Hom.:

Cov.:

AF XY:

0.0000589

AC XY:

AN XY:

33950

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30771

American (AMR)

AF:

0.0000958

AC:

AN:

10441

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3590

South Asian (SAS)

AF:

0.00

AC:

AN:

2676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6027

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53194

Other (OTH)

AF:

0.000672

AC:

AN:

1489

Age Distribution

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:

0.00

Hom.:

Bravo

AF:

0.0000113

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

Uncertain

0.41

BayesDel_addAF

Uncertain

0.055

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.83

PhyloP100

7.5

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.59

MutPred

0.58

Gain of methylation at K675 (P = 0.0286)

MVP

0.67

MPC

0.99

ClinPred

0.87

GERP RS

3.1

Varity_R

0.83

gMVP

0.60

Mutation Taster

=88/12

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