X-17750159-A-C

Variant names:

• chrX-17750159-A-C
• rs757689442
• NM_001037540.3:c.569A>C

Variant summary

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

The NM_001037540.3(SCML1):​c.569A>C​(p.His190Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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. H190R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 24)
• Consequence: SCML1 NM_001037540.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919
• Publications: 0 publications found

Genes affected

SCML1 (HGNC:10580): (Scm polycomb group protein like 1) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.07326794).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037540.3. 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
	SCML1	NM_001037540.3	MANE Select	c.569A>C	p.His190Pro	missense	Exon 6 of 8	NP_001032629.1	Q9UN30-3
	SCML1	NM_006746.6		c.488A>C	p.His163Pro	missense	Exon 5 of 7	NP_006737.2	Q9UN30-2
	SCML1	NM_001037535.3		c.206A>C	p.His69Pro	missense	Exon 4 of 6	NP_001032624.1	Q9UN30-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCML1	ENST00000380041.8	TSL:5 MANE Select	c.569A>C	p.His190Pro	missense	Exon 6 of 8	ENSP00000369380.3	Q9UN30-3
	SCML1	ENST00000380043.7	TSL:1	c.488A>C	p.His163Pro	missense	Exon 5 of 7	ENSP00000369382.3	Q9UN30-2
	SCML1	ENST00000380045.7	TSL:1	c.206A>C	p.His69Pro	missense	Exon 4 of 6	ENSP00000369384.3	Q9UN30-1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

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	0.075
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.70
DEOGEN2	Benign	0.029	T
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.92
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.0070
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.028	D
Polyphen		0.024	B
Vest4		0.091
MutPred		0.26		Gain of relative solvent accessibility (P = 0.0249)
MVP		0.068
MPC		1.4
ClinPred		0.11	T
GERP RS		-5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.13
Mutation Taster		=97/3	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: rs757689442; hg19: chrX-17768279;