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GeneBe

X-18265733-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_006089.3(SCML2):c.800C>T(p.Ser267Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

SCML2
NM_006089.3 missense

Scores

6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.09
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity SCML2_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27464035).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCML2NM_006089.3 linkuse as main transcriptc.800C>T p.Ser267Phe missense_variant 8/15 ENST00000251900.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCML2ENST00000251900.9 linkuse as main transcriptc.800C>T p.Ser267Phe missense_variant 8/151 NM_006089.3 P1Q9UQR0-1
SCML2ENST00000665583.1 linkuse as main transcriptc.8C>T p.Ser3Phe missense_variant 2/8

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
23

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 GeneticsJun 01, 2023The c.800C>T (p.S267F) alteration is located in exon 8 (coding exon 7) of the SCML2 gene. This alteration results from a C to T substitution at nucleotide position 800, causing the serine (S) at amino acid position 267 to be replaced by a phenylalanine (F). 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
0.12
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
Cadd
Uncertain
23
Dann
Uncertain
1.0
DEOGEN2
Benign
0.18
T
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
0.98
D;D
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-4.2
D
REVEL
Benign
0.18
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.010
D
Polyphen
0.92
P
Vest4
0.33
MutPred
0.17
Loss of phosphorylation at S267 (P = 0.0339);
MVP
0.18
MPC
1.5
ClinPred
0.97
D
GERP RS
4.8
Varity_R
0.56
gMVP
0.55

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-18283853; COSMIC: COSV104574358; API