rs6654021

Positions:

• chrX-17737888-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037540.3(SCML1):​c.-117+208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 111,037 control chromosomes in the GnomAD database, including 2,945 homozygotes. There are 4,508 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2945 hom., 4507 hem., cov: 22)
  • Exomes 𝑓: 0.045 (0 hom. 1 hem.)
• Consequence: SCML1 NM_001037540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCML1	NM_001037540.3	c.-117+208A>G		intron_variant		ENST00000380041.8	NP_001032629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCML1	ENST00000380041.8	c.-117+208A>G		intron_variant		5	NM_001037540.3	ENSP00000369380	A2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 17055 AN: 110960 Hom.: 2944 Cov.: 22 AF XY: 0.134 AC XY: 4468 AN XY: 33222

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.00294

Gnomad AMR AF: 0.0717

Gnomad ASJ AF: 0.0117

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00829

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.0455 AC: 1 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0526

GnomAD4 genome AF: 0.154 AC: 17098 AN: 111015 Hom.: 2945 Cov.: 22 AF XY: 0.135 AC XY: 4507 AN XY: 33287

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.0716

Gnomad4 ASJ AF: 0.0117

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00831

Gnomad4 FIN AF: 0.0103

Gnomad4 NFE AF: 0.0162

Gnomad4 OTH AF: 0.141

Alfa AF: 0.0492 Hom.: 1090

Bravo AF: 0.178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.46

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: rs6654021; hg19: chrX-17756008;