rs6654021

Variant names:

• chrX-17737888-A-G
• rs6654021
• NM_001037540.3:c.-117+208A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
SCML1	NM_001037540.3	c.-117+208A>G		intron_variant	Intron 1 of 7	ENST00000380041.8	NP_001032629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCML1	ENST00000380041.8	c.-117+208A>G		intron_variant	Intron 1 of 7	5	NM_001037540.3	ENSP00000369380.3

Frequencies

GnomAD3 genomes AF: 0.154 AC: 17055 AN: 110960 Hom.: 2944 Cov.: 22

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 1

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0526 AC: 1 AN: 19

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.501 AC: 15130 AN: 30184

American (AMR) AF: 0.0716 AC: 756 AN: 10563

Ashkenazi Jewish (ASJ) AF: 0.0117 AC: 31 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3513

South Asian (SAS) AF: 0.00831 AC: 22 AN: 2648

European-Finnish (FIN) AF: 0.0103 AC: 62 AN: 6004

Middle Eastern (MID) AF: 0.113 AC: 24 AN: 213

European-Non Finnish (NFE) AF: 0.0162 AC: 860 AN: 53057

Other (OTH) AF: 0.141 AC: 211 AN: 1501

Alfa AF: 0.0474 Hom.: 1155

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
PhyloP100		1.2
PromoterAI		-0.033	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs6654021; hg19: chrX-17756008;