rs757689442

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-17750159-A-C
• chrX-17750159-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07326794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCML1	NM_001037540.3	c.569A>C	p.His190Pro	missense_variant	Exon 6 of 8	ENST00000380041.8	NP_001032629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCML1	ENST00000380041.8	c.569A>C	p.His190Pro	missense_variant	Exon 6 of 8	5	NM_001037540.3	ENSP00000369380.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.073	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	.;.;L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.0070
Sift	Uncertain	0.012	D;D;D;D
Sift4G	Uncertain	0.028	D;D;D;D
Polyphen		0.024, 0.041	.;.;B;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

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

LitVar

Other links and lift over

dbSNP: rs757689442; hg19: chrX-17768279;