X-18258073-G-C

Variant summary

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

The NM_006089.3(SCML2):ā€‹c.1244C>Gā€‹(p.Pro415Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,208,030 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000045 ( 0 hom., 1 hem., cov: 21)
Exomes š‘“: 0.000024 ( 0 hom. 7 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73
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=0.018807739).
BS2
High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SCML2NM_006089.3 linkc.1244C>G p.Pro415Arg missense_variant 10/15 ENST00000251900.9 NP_006080.1 Q9UQR0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SCML2ENST00000251900.9 linkc.1244C>G p.Pro415Arg missense_variant 10/151 NM_006089.3 ENSP00000251900.4 Q9UQR0-1
SCML2ENST00000665583.1 linkc.452C>G p.Pro151Arg missense_variant 4/8 ENSP00000499630.1 B4DRC2

Frequencies

GnomAD3 genomes
AF:
0.0000451
AC:
5
AN:
110807
Hom.:
0
Cov.:
21
AF XY:
0.0000303
AC XY:
1
AN XY:
32993
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:
0.00143
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000709
AC:
13
AN:
183446
Hom.:
0
AF XY:
0.0000442
AC XY:
3
AN XY:
67878
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000938
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000237
AC:
26
AN:
1097177
Hom.:
0
Cov.:
30
AF XY:
0.0000193
AC XY:
7
AN XY:
362551
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000762
Gnomad4 SAS exome
AF:
0.0000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000434
GnomAD4 genome
AF:
0.0000451
AC:
5
AN:
110853
Hom.:
0
Cov.:
21
AF XY:
0.0000303
AC XY:
1
AN XY:
33049
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00144
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000793
ExAC
AF:
0.0000906
AC:
11

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 GeneticsDec 17, 2023The c.1244C>G (p.P415R) 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 1244, causing the proline (P) at amino acid position 415 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
Benign
0.28
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.044
T
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.019
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-2.5
N
REVEL
Benign
0.055
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.014
D
Polyphen
0.10
B
Vest4
0.26
MutPred
0.30
Loss of loop (P = 0.0374);
MVP
0.26
MPC
1.2
ClinPred
0.18
T
GERP RS
4.5
Varity_R
0.29
gMVP
0.30

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: rs779557253; hg19: chrX-18276193; API