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GeneBe

X-18260224-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006089.3(SCML2):c.1016G>A(p.Gly339Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,088,801 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

SCML2
NM_006089.3 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.434
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.092320025).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCML2NM_006089.3 linkuse as main transcriptc.1016G>A p.Gly339Asp missense_variant 9/15 ENST00000251900.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCML2ENST00000251900.9 linkuse as main transcriptc.1016G>A p.Gly339Asp missense_variant 9/151 NM_006089.3 P1Q9UQR0-1
SCML2ENST00000665583.1 linkuse as main transcriptc.224G>A p.Gly75Asp missense_variant 3/8

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
0.00000184
AC:
2
AN:
1088801
Hom.:
0
Cov.:
26
AF XY:
0.00000282
AC XY:
1
AN XY:
354999
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:
0.0000376
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22

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 GeneticsOct 06, 2022The c.1016G>A (p.G339D) alteration is located in exon 9 (coding exon 8) of the SCML2 gene. This alteration results from a G to A substitution at nucleotide position 1016, causing the glycine (G) at amino acid position 339 to be replaced by an aspartic acid (D). 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
0.083
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.80
Cadd
Benign
4.6
Dann
Benign
0.88
DEOGEN2
Benign
0.035
T
FATHMM_MKL
Benign
0.040
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.092
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.70
N
REVEL
Benign
0.049
Sift
Benign
0.14
T
Sift4G
Benign
0.43
T
Polyphen
0.022
B
Vest4
0.20
MutPred
0.47
Gain of ubiquitination at K343 (P = 0.0444);
MVP
0.093
MPC
0.78
ClinPred
0.12
T
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.10
gMVP
0.39

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-18278344; API