X-18246674-TC-GA

Variant names:

• chrX-18246674-TC-GA
• NM_006089.3:c.1724_1725delGAinsTC
• SCML2 p.Arg575Leu

Variant summary

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

The NM_006089.3(SCML2):​c.1724_1725delGAinsTC​(p.Arg575Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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: 22)
• 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.

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.1724_1725delGAinsTC	p.Arg575Leu	missense	N/A	NP_006080.1	Q9UQR0-1
	SCML2	NR_033717.2		n.1845_1846delGAinsTC		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.1724_1725delGAinsTC	p.Arg575Leu	missense	N/A	ENSP00000251900.4	Q9UQR0-1
	SCML2	ENST00000398048.4	TSL:1	c.38_39delGAinsTC	p.Arg13Leu	missense	N/A	ENSP00000381126.4	Q9UQR0-2
	SCML2	ENST00000926833.1		c.1724_1725delGAinsTC	p.Arg575Leu	missense	N/A	ENSP00000596892.1

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-18264794;