X-17750120-G-T

Variant names:

• chrX-17750120-G-T
• rs371840167
• NM_001037540.3:c.530G>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.530G>T​(p.Arg177Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 112,298 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. 14/19 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: 𝑓 0.0000089 (0 hom., 1 hem., cov: 24)
• Consequence: SCML1 NM_001037540.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

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=0.06233424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCML1	NM_001037540.3	c.530G>T	p.Arg177Leu	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.530G>T	p.Arg177Leu	missense_variant	Exon 6 of 8	5	NM_001037540.3	ENSP00000369380.3

Frequencies

GnomAD3 genomes AF: 0.00000890 AC: 1 AN: 112298 Hom.: 0 Cov.: 24 AF XY: 0.0000290 AC XY: 1 AN XY: 34456

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000547 AC: 1 AN: 182974 Hom.: 0 AF XY: 0.0000148 AC XY: 1 AN XY: 67520

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000890 AC: 1 AN: 112298 Hom.: 0 Cov.: 24 AF XY: 0.0000290 AC XY: 1 AN XY: 34456

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.20
DANN	Benign	0.23
DEOGEN2	Benign	0.033	.;.;T;.
FATHMM_MKL	Benign	0.00078	N
LIST_S2	Benign	0.59	T;.;T;T
M_CAP	Benign	0.00057	T
MetaRNN	Benign	0.062	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;.;N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.92	N;N;N;N
REVEL	Benign	0.0060
Sift	Benign	0.16	T;T;T;T
Sift4G	Benign	0.64	T;T;T;T
Polyphen		0.0010, 0.0020	.;.;B;B
Vest4		0.059
MutPred		0.29		.;.;Gain of glycosylation at S180 (P = 0.108);.;
MVP		0.043
MPC		1.2
ClinPred		0.047	T
GERP RS		-6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.13

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: rs371840167; hg19: chrX-17768240;