X-18257008-A-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006089.3(SCML2):āc.1296T>Gā(p.His432Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000021 in 1,188,259 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000090 ( 0 hom., 0 hem., cov: 22)
Exomes š: 0.000022 ( 0 hom. 13 hem. )
Consequence
SCML2
NM_006089.3 missense
NM_006089.3 missense
Scores
3
6
8
Clinical Significance
Conservation
PhyloP100: 0.316
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 Likely_benign. Variant got -4 ACMG points.
BS2
High Hemizygotes in GnomAdExome4 at 13 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCML2 | NM_006089.3 | c.1296T>G | p.His432Gln | missense_variant | 11/15 | ENST00000251900.9 | NP_006080.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCML2 | ENST00000251900.9 | c.1296T>G | p.His432Gln | missense_variant | 11/15 | 1 | NM_006089.3 | ENSP00000251900.4 | ||
SCML2 | ENST00000665583.1 | c.504T>G | p.His168Gln | missense_variant | 5/8 | ENSP00000499630.1 |
Frequencies
GnomAD3 genomes AF: 0.00000896 AC: 1AN: 111550Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33728
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GnomAD3 exomes AF: 0.00000628 AC: 1AN: 159340Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 48386
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GnomAD4 exome AF: 0.0000223 AC: 24AN: 1076709Hom.: 0 Cov.: 28 AF XY: 0.0000376 AC XY: 13AN XY: 345899
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GnomAD4 genome AF: 0.00000896 AC: 1AN: 111550Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33728
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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 | Feb 16, 2023 | The c.1296T>G (p.H432Q) alteration is located in exon 11 (coding exon 10) of the SCML2 gene. This alteration results from a T to G substitution at nucleotide position 1296, causing the histidine (H) at amino acid position 432 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of sheet (P = 0.0344);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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