dbSNP rs767496928: SCML1:p.Asn38Ser (chrX-17745535-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001037540.3(SCML1):c.113A>G(p.Asn38Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,096,440 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict 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: 23)

Exomes 𝑓: 0.0000041 ( 0 hom. 2 hem. )

Consequence

SCML1
NM_001037540.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.593

Publications

0 publications found

Variant links:

Genes affected

SCML1 (HGNC:10580): (Scm polycomb group protein like 1) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SCML1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038914293).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037540.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCML1	NM_001037540.3	MANE Select	c.113A>G	p.Asn38Ser	missense	Exon 3 of 8	NP_001032629.1	Q9UN30-3
SCML1	NM_006746.6		c.34-480A>G		intron	N/A	NP_006737.2	Q9UN30-2
SCML1	NM_001037535.3		c.-249-480A>G		intron	N/A	NP_001032624.1	Q9UN30-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCML1	ENST00000380041.8	TSL:5 MANE Select	c.113A>G	p.Asn38Ser	missense	Exon 3 of 8	ENSP00000369380.3	Q9UN30-3
SCML1	ENST00000380043.7	TSL:1	c.34-480A>G		intron	N/A	ENSP00000369382.3	Q9UN30-2
SCML1	ENST00000380045.7	TSL:1	c.-246-483A>G		intron	N/A	ENSP00000369384.3	Q9UN30-1

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112330

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

GnomAD2 exomes

AF:

0.0000123

AC:

AN:

162521

AF XY:

0.0000195

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000406

AC:

AN:

984110

Hom.:

Cov.:

AF XY:

0.00000716

AC XY:

AN XY:

279234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23707

American (AMR)

AF:

0.00

AC:

AN:

31282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18251

East Asian (EAS)

AF:

0.0000682

AC:

AN:

29306

South Asian (SAS)

AF:

0.0000206

AC:

AN:

48648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40261

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3853

European-Non Finnish (NFE)

AF:

0.00000134

AC:

AN:

746570

Other (OTH)

AF:

0.00

AC:

AN:

42232

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

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:

0.00000890

AC:

AN:

112330

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30935

American (AMR)

AF:

0.00

AC:

AN:

10607

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3618

South Asian (SAS)

AF:

0.00

AC:

AN:

2736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6141

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53208

Other (OTH)

AF:

0.00

AC:

AN:

1515

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

0.077

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.70

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.019

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.48

M_CAP

Benign

0.0028

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.63

PhyloP100

-0.59

PROVEAN

Benign

-0.76

REVEL

Benign

0.014

Sift

Benign

0.26

Sift4G

Benign

0.24

Polyphen

0.064

Vest4

0.053

MutPred

0.31

Gain of glycosylation at N38 (P = 0.0376)

MVP

0.12

MPC

0.75

ClinPred

0.056

GERP RS

-6.2

Varity_R

0.037

gMVP

0.021

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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