rs1228987621

Variant names:

• chrX-18258157-G-A
• NM_006089.3:c.1160C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-18258157-G-A
• chrX-18258157-G-C
• chrX-18258157-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006089.3(SCML2):​c.1160C>T​(p.Pro387Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,764 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: SCML2 NM_006089.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.30

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCML2	NM_006089.3	c.1160C>T	p.Pro387Leu	missense_variant	Exon 10 of 15	ENST00000251900.9	NP_006080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCML2	ENST00000251900.9	c.1160C>T	p.Pro387Leu	missense_variant	Exon 10 of 15	1	NM_006089.3	ENSP00000251900.4
SCML2	ENST00000665583.1	c.368C>T	p.Pro123Leu	missense_variant	Exon 4 of 8			ENSP00000499630.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097764 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363122

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.30
Sift	Benign	0.060	T
Sift4G	Uncertain	0.024	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.43		Gain of helix (P = 0.062);
MVP		0.44
MPC		1.5
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.32
gMVP		0.81

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-18276277; COSMIC: COSV104382043;