X-18246675-C-A

Variant names:

• chrX-18246675-C-A
• rs747463983
• NM_006089.3:c.1724G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006089.3(SCML2):​c.1724G>T​(p.Arg575Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,096,954 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R575Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000036 (0 hom. 0 hem.)
• Consequence: SCML2 NM_006089.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09777433).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006089.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCML2	NM_006089.3	MANE Select	c.1724G>T	p.Arg575Leu	missense	Exon 13 of 15	NP_006080.1	Q9UQR0-1
	SCML2	NR_033717.2		n.1845G>T		non_coding_transcript_exon	Exon 13 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCML2	ENST00000251900.9	TSL:1 MANE Select	c.1724G>T	p.Arg575Leu	missense	Exon 13 of 15	ENSP00000251900.4	Q9UQR0-1
	SCML2	ENST00000398048.4	TSL:1	c.38G>T	p.Arg13Leu	missense	Exon 1 of 4	ENSP00000381126.4	Q9UQR0-2
	SCML2	ENST00000926833.1		c.1724G>T	p.Arg575Leu	missense	Exon 13 of 15	ENSP00000596892.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1096954 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 362328

African (AFR) AF: 0.00 AC: 0 AN: 26379

American (AMR) AF: 0.00 AC: 0 AN: 35194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19379

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.00 AC: 0 AN: 54098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40525

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00000476 AC: 4 AN: 841006

Other (OTH) AF: 0.00 AC: 0 AN: 46046

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.044	T
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.28
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.077
Sift	Benign	0.051	T
Sift4G	Benign	0.29	T
Polyphen		0.26	B
Vest4		0.070
MutPred		0.29		Loss of phosphorylation at S576 (P = 0.1092)
MVP		0.068
MPC		0.73
ClinPred		0.17	T
GERP RS		0.15
PromoterAI		-0.0064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.38
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs747463983; hg19: chrX-18264795;