chrX-18260224-C-T

Variant names:

• chrX-18260224-C-T
• NM_006089.3:c.1016G>A

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.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. 15/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.434
• 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=0.092320025).

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.1016G>A	p.Gly339Asp	missense	Exon 9 of 15	NP_006080.1
	SCML2	NR_033717.2		n.1137G>A		non_coding_transcript_exon	Exon 9 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCML2	ENST00000251900.9	TSL:1 MANE Select	c.1016G>A	p.Gly339Asp	missense	Exon 9 of 15	ENSP00000251900.4
	SCML2	ENST00000926833.1		c.1016G>A	p.Gly339Asp	missense	Exon 9 of 15	ENSP00000596892.1
	SCML2	ENST00000926834.1		c.1016G>A	p.Gly339Asp	missense	Exon 10 of 16	ENSP00000596893.1

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

African (AFR) AF: 0.00 AC: 0 AN: 26222

American (AMR) AF: 0.00 AC: 0 AN: 35063

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19247

East Asian (EAS) AF: 0.00 AC: 0 AN: 30113

South Asian (SAS) AF: 0.0000376 AC: 2 AN: 53249

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4100

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 834694

Other (OTH) AF: 0.00 AC: 0 AN: 45719

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.43
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
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

hg19: chrX-18278344; COSMIC: COSV106349583;