Variant X-17749482-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001037540.3(SCML1):c.281C>T(p.Ala94Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,167,932 control chromosomes in the GnomAD database, including 8 homozygotes. There are 392 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., 78 hem., cov: 24)

Exomes 𝑓: 0.0011 ( 6 hom. 314 hem. )

Consequence

SCML1
NM_001037540.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.39

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050575435).

BP6

Variant X-17749482-C-T is Benign according to our data. Variant chrX-17749482-C-T is described in ClinVar as [Benign]. Clinvar id is 720065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00111 (1170/1055775) while in subpopulation AMR AF= 0.0199 (666/33391). AF 95% confidence interval is 0.0187. There are 6 homozygotes in gnomad4_exome. There are 314 alleles in male gnomad4_exome subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCML1	NM_001037540.3 linkuse as main transcript	c.281C>T	p.Ala94Val	missense_variant	5/8	ENST00000380041.8	NP_001032629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCML1	ENST00000380041.8 linkuse as main transcript	c.281C>T	p.Ala94Val	missense_variant	5/8	5	NM_001037540.3	ENSP00000369380	A2	Q9UN30-3

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

238

AN:

112106

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

AN XY:

34292

show subpopulations

Gnomad AFR

AF:

0.000812

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00829

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00149

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00265

GnomAD3 exomes

AF:

0.00380

AC:

660

AN:

173701

Hom.:

AF XY:

0.00208

AC XY:

124

AN XY:

59565

show subpopulations

Gnomad AFR exome

AF:

0.000464

Gnomad AMR exome

AF:

0.0196

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00919

Gnomad SAS exome

AF:

0.0000612

Gnomad FIN exome

AF:

0.00133

Gnomad NFE exome

AF:

0.0000882

Gnomad OTH exome

AF:

0.00353

GnomAD4 exome

AF:

0.00111

AC:

1170

AN:

1055775

Hom.:

Cov.:

AF XY:

0.000962

AC XY:

314

AN XY:

326393

show subpopulations

Gnomad4 AFR exome

AF:

0.000551

Gnomad4 AMR exome

AF:

0.0199

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0101

Gnomad4 SAS exome

AF:

0.0000390

Gnomad4 FIN exome

AF:

0.00191

Gnomad4 NFE exome

AF:

0.0000421

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00214

AC:

240

AN:

112157

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

AN XY:

34353

show subpopulations

Gnomad4 AFR

AF:

0.000811

Gnomad4 AMR

AF:

0.0158

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00804

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00149

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.00262

Alfa

AF:

0.000758

Hom.:

Bravo

AF:

0.00311

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.00288

AC:

350

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0010

DANN

Benign

0.67

DEOGEN2

Benign

0.012

T;.;.

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.57

T;T;T

MetaRNN

Benign

0.0051

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.14

N;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.37

N;N;N

REVEL

Benign

0.017

Sift

Benign

0.22

T;T;T

Sift4G

Benign

0.40

T;T;T

Polyphen

0.31

B;B;.

Vest4

0.060

MVP

0.12

MPC

0.93

ClinPred

0.0050

GERP RS

-4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.031

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over