X-18256934-T-C
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_006089.3(SCML2):āc.1370A>Gā(p.Gln457Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000302 in 1,206,708 control chromosomes in the GnomAD database, including 2 homozygotes. There are 111 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00038 ( 1 hom., 11 hem., cov: 23)
Exomes š: 0.00029 ( 1 hom. 100 hem. )
Consequence
SCML2
NM_006089.3 missense
NM_006089.3 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 5.88
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 Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0100007355).
BS2
?
High Hemizygotes in GnomAd4 at 11 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCML2 | NM_006089.3 | c.1370A>G | p.Gln457Arg | missense_variant | 11/15 | ENST00000251900.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCML2 | ENST00000251900.9 | c.1370A>G | p.Gln457Arg | missense_variant | 11/15 | 1 | NM_006089.3 | P1 | |
SCML2 | ENST00000665583.1 | c.578A>G | p.Gln193Arg | missense_variant | 5/8 |
Frequencies
GnomAD3 genomes ? AF: 0.000384 AC: 43AN: 111896Hom.: 1 Cov.: 23 AF XY: 0.000323 AC XY: 11AN XY: 34062
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GnomAD3 exomes AF: 0.000458 AC: 82AN: 179020Hom.: 0 AF XY: 0.000675 AC XY: 43AN XY: 63750
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GnomAD4 exome AF: 0.000293 AC: 321AN: 1094761Hom.: 1 Cov.: 28 AF XY: 0.000278 AC XY: 100AN XY: 360341
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GnomAD4 genome ? AF: 0.000384 AC: 43AN: 111947Hom.: 1 Cov.: 23 AF XY: 0.000322 AC XY: 11AN XY: 34123
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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 submitter | clinical testing | Ambry Genetics | Oct 05, 2021 | The c.1370A>G (p.Q457R) 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 1370, causing the glutamine (Q) at amino acid position 457 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at