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GeneBe

X-18324029-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006089.3(SCML2):c.227A>G(p.Asn76Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000463 in 1,209,076 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 2 hem., cov: 22)
Exomes 𝑓: 0.000047 ( 0 hom. 16 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

4
3
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.20418325).
BS2
High Hemizygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCML2NM_006089.3 linkuse as main transcriptc.227A>G p.Asn76Ser missense_variant 5/15 ENST00000251900.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCML2ENST00000251900.9 linkuse as main transcriptc.227A>G p.Asn76Ser missense_variant 5/151 NM_006089.3 P1Q9UQR0-1

Frequencies

GnomAD3 genomes
AF:
0.0000360
AC:
4
AN:
111202
Hom.:
0
Cov.:
22
AF XY:
0.0000599
AC XY:
2
AN XY:
33384
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000194
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:
0.0000377
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000213
AC:
39
AN:
183442
Hom.:
0
AF XY:
0.000147
AC XY:
10
AN XY:
67880
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00128
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000525
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000244
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.0000474
AC:
52
AN:
1097874
Hom.:
0
Cov.:
30
AF XY:
0.0000440
AC XY:
16
AN XY:
363232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00122
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000713
Gnomad4 OTH exome
AF:
0.0000434
GnomAD4 genome
AF:
0.0000360
AC:
4
AN:
111202
Hom.:
0
Cov.:
22
AF XY:
0.0000599
AC XY:
2
AN XY:
33384
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000194
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000377
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000127
Hom.:
1
Bravo
AF:
0.0000982
ExAC
AF:
0.000165
AC:
20
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

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 GeneticsApr 13, 2022The c.227A>G (p.N76S) alteration is located in exon 5 (coding exon 4) of the SCML2 gene. This alteration results from a A to G substitution at nucleotide position 227, causing the asparagine (N) at amino acid position 76 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
0.15
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.59
Cadd
Benign
20
Dann
Uncertain
1.0
DEOGEN2
Benign
0.16
T
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.44
T
MutationAssessor
Uncertain
2.7
M
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-4.9
D
REVEL
Benign
0.28
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.37
MutPred
0.62
Gain of disorder (P = 0.0936);
MVP
0.77
MPC
0.62
ClinPred
0.26
T
GERP RS
4.6
Varity_R
0.90
gMVP
0.77

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: rs766427319; hg19: chrX-18342149; API