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GeneBe

X-17745535-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

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. 13/18 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

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.593
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.038914293).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCML1NM_001037540.3 linkuse as main transcriptc.113A>G p.Asn38Ser missense_variant 3/8 ENST00000380041.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCML1ENST00000380041.8 linkuse as main transcriptc.113A>G p.Asn38Ser missense_variant 3/85 NM_001037540.3 A2Q9UN30-3

Frequencies

GnomAD3 genomes
AF:
0.00000890
AC:
1
AN:
112330
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34502
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
GnomAD3 exomes
AF:
0.0000123
AC:
2
AN:
162521
Hom.:
0
AF XY:
0.0000195
AC XY:
1
AN XY:
51281
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000406
AC:
4
AN:
984110
Hom.:
0
Cov.:
17
AF XY:
0.00000716
AC XY:
2
AN XY:
279234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000682
Gnomad4 SAS exome
AF:
0.0000206
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000134
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000890
AC:
1
AN:
112330
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34502
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 16, 2023The c.113A>G (p.N38S) alteration is located in exon 3 (coding exon 2) of the SCML1 gene. This alteration results from a A to G substitution at nucleotide position 113, causing the asparagine (N) at amino acid position 38 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.98
Cadd
Benign
0.70
Dann
Benign
0.90
DEOGEN2
Benign
0.019
T
FATHMM_MKL
Benign
0.0036
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.0028
T
MetaRNN
Benign
0.039
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.63
N
MutationTaster
Benign
1.0
N;N;N;N
PROVEAN
Benign
-0.76
N
REVEL
Benign
0.014
Sift
Benign
0.26
T
Sift4G
Benign
0.24
T
Polyphen
0.064
B
Vest4
0.053
MutPred
0.31
Gain of glycosylation at N38 (P = 0.0376);
MVP
0.12
MPC
0.75
ClinPred
0.056
T
GERP RS
-6.2
Varity_R
0.037
gMVP
0.021

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

LitVar

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

Other links and lift over

dbSNP: rs767496928; hg19: chrX-17763655; API