Menu
GeneBe

X-18258157-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006089.3(SCML2):c.1160C>G(p.Pro387Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000165 in 1,209,571 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

3
2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.30
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29480153).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCML2NM_006089.3 linkuse as main transcriptc.1160C>G p.Pro387Arg missense_variant 10/15 ENST00000251900.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCML2ENST00000251900.9 linkuse as main transcriptc.1160C>G p.Pro387Arg missense_variant 10/151 NM_006089.3 P1Q9UQR0-1
SCML2ENST00000665583.1 linkuse as main transcriptc.368C>G p.Pro123Arg missense_variant 4/8

Frequencies

GnomAD3 genomes
AF:
0.00000894
AC:
1
AN:
111807
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33969
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1097764
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
363122
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:
0.00
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.00000894
AC:
1
AN:
111807
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33969
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000756

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 GeneticsFeb 17, 2024The c.1160C>G (p.P387R) alteration is located in exon 10 (coding exon 9) of the SCML2 gene. This alteration results from a C to G substitution at nucleotide position 1160, causing the proline (P) at amino acid position 387 to be replaced by an arginine (R). 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
Pathogenic
0.80
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
Cadd
Benign
22
Dann
Benign
0.85
DEOGEN2
Benign
0.17
T
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.29
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.2
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-4.6
D
REVEL
Uncertain
0.29
Sift
Benign
0.84
T
Sift4G
Benign
0.39
T
Polyphen
0.83
P
Vest4
0.35
MutPred
0.50
Gain of sheet (P = 0.0061);
MVP
0.36
MPC
1.1
ClinPred
0.91
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.40
gMVP
0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1228987621; hg19: chrX-18276277; API