rs757689442

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001037540.3(SCML1):​c.569A>G​(p.His190Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,196 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: SCML1 NM_001037540.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062244534).

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>G	p.His190Arg	missense	Exon 6 of 8	NP_001032629.1	Q9UN30-3
	SCML1	NM_006746.6		c.488A>G	p.His163Arg	missense	Exon 5 of 7	NP_006737.2	Q9UN30-2
	SCML1	NM_001037535.3		c.206A>G	p.His69Arg	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>G	p.His190Arg	missense	Exon 6 of 8	ENSP00000369380.3	Q9UN30-3
	SCML1	ENST00000380043.7	TSL:1	c.488A>G	p.His163Arg	missense	Exon 5 of 7	ENSP00000369382.3	Q9UN30-2
	SCML1	ENST00000380045.7	TSL:1	c.206A>G	p.His69Arg	missense	Exon 4 of 6	ENSP00000369384.3	Q9UN30-1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 182992 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098196 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363552

African (AFR) AF: 0.00 AC: 0 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54147

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842086

Other (OTH) AF: 0.00 AC: 0 AN: 46094

GnomAD4 genome Cov.: 24

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

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	0.072
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.55
DANN	Benign	0.56
DEOGEN2	Benign	0.020	T
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.11	N
PhyloP100		-0.92
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.017
Sift	Benign	0.15	T
Sift4G	Benign	0.14	T
Polyphen		0.024	B
Vest4		0.048
MutPred		0.26		Gain of solvent accessibility (P = 0.0704)
MVP		0.10
MPC		1.3
ClinPred		0.070	T
GERP RS		-5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.084
Mutation Taster		=100/0	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;