rs746477197

Variant names:

• chrX-17750026-C-G
• NM_001037540.3:c.436C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-17750026-C-G
• chrX-17750026-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001037540.3(SCML1):​c.436C>G​(p.Arg146Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000455 in 1,098,039 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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: 23)
  • Exomes 𝑓: 0.0000046 (0 hom. 1 hem.)
• Consequence: SCML1 NM_001037540.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06579295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCML1	NM_001037540.3	c.436C>G	p.Arg146Gly	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.436C>G	p.Arg146Gly	missense_variant	Exon 6 of 8	5	NM_001037540.3	ENSP00000369380.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000455 AC: 5 AN: 1098039 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363395

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000594

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.32
DANN	Benign	0.68
DEOGEN2	Benign	0.048	.;.;T;.;.
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.55	T;.;T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.066	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	.;.;L;.;.
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.6	N;N;N;N;D
REVEL	Benign	0.047
Sift	Benign	0.20	T;T;T;T;T
Sift4G	Benign	0.18	T;T;T;T;T
Polyphen		0.96, 0.97	.;.;P;D;.
Vest4		0.063
MutPred		0.22		.;.;Loss of solvent accessibility (P = 0.0159);.;.;
MVP		0.068
MPC		1.3
ClinPred		0.19	T
GERP RS		0.63
Varity_R		0.082
gMVP		0.095

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-17768146;