rs142861368

Variant names:

• chrX-17749482-C-G
• rs142861368
• NM_001037540.3:c.281C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-17749482-C-G
• chrX-17749482-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037540.3(SCML1):​c.281C>G​(p.Ala94Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000947 in 1,055,800 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. 13/19 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)
  • Exomes 𝑓: 9.5e-7 (0 hom. 0 hem.)
• Consequence: SCML1 NM_001037540.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39

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=0.10529405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCML1	NM_001037540.3	c.281C>G	p.Ala94Gly	missense_variant	Exon 5 of 8	ENST00000380041.8	NP_001032629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCML1	ENST00000380041.8	c.281C>G	p.Ala94Gly	missense_variant	Exon 5 of 8	5	NM_001037540.3	ENSP00000369380.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000576 AC: 1 AN: 173701 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 59565

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000402

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.47e-7 AC: 1 AN: 1055800 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 326398

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000299

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.0010
DANN	Benign	0.85
DEOGEN2	Benign	0.025	T;.;.
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.3	N;N;D
REVEL	Benign	0.075
Sift	Uncertain	0.013	D;D;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.92	P;P;.
Vest4		0.13
MutPred		0.33		Loss of helix (P = 0.0033);.;.;
MVP		0.12
MPC		1.0
ClinPred		0.14	T
GERP RS		-4.2
Varity_R		0.076
gMVP		0.038

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: rs142861368; hg19: chrX-17767602;