X-18256860-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006089.3(SCML2):ā€‹c.1444A>Gā€‹(p.Lys482Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000075 in 1,067,368 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 22)
Exomes š‘“: 0.0000075 ( 0 hom. 2 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.05207455).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCML2NM_006089.3 linkuse as main transcriptc.1444A>G p.Lys482Glu missense_variant 11/15 ENST00000251900.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCML2ENST00000251900.9 linkuse as main transcriptc.1444A>G p.Lys482Glu missense_variant 11/151 NM_006089.3 P1Q9UQR0-1
SCML2ENST00000665583.1 linkuse as main transcriptc.652A>G p.Lys218Glu missense_variant 5/8

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
0.00000750
AC:
8
AN:
1067368
Hom.:
0
Cov.:
28
AF XY:
0.00000582
AC XY:
2
AN XY:
343656
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000963
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22

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 GeneticsJan 18, 2022The c.1444A>G (p.K482E) alteration is located in exon 11 (coding exon 10) of the SCML2 gene. This alteration results from a A to G substitution at nucleotide position 1444, causing the lysine (K) at amino acid position 482 to be replaced by a glutamic acid (E). 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
0.079
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.92
CADD
Benign
2.3
DANN
Benign
0.85
DEOGEN2
Benign
0.018
T
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.0080
T
MetaRNN
Benign
0.052
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.39
N
REVEL
Benign
0.028
Sift
Benign
0.088
T
Sift4G
Benign
0.18
T
Polyphen
0.0020
B
Vest4
0.096
MutPred
0.27
Loss of ubiquitination at K482 (P = 9e-04);
MVP
0.15
MPC
0.86
ClinPred
0.059
T
GERP RS
-3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.072
gMVP
0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-18274980; API