X-17749482-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001037540.3(SCML1):c.281C>T(p.Ala94Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,167,932 control chromosomes in the GnomAD database, including 8 homozygotes. There are 392 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., 78 hem., cov: 24)
  • Exomes 𝑓: 0.0011 (6 hom. 314 hem.)
• Consequence: SCML1 NM_001037540.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050575435).
• BP6: Variant X-17749482-C-T is Benign according to our data. Variant chrX-17749482-C-T is described in ClinVar as [Benign]. Clinvar id is 720065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00111 (1170/1055775) while in subpopulation AMR AF= 0.0199 (666/33391). AF 95% confidence interval is 0.0187. There are 6 homozygotes in gnomad4_exome. There are 314 alleles in male gnomad4_exome subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCML1	NM_001037540.3	c.281C>T	p.Ala94Val	missense_variant	5/8	ENST00000380041.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCML1	ENST00000380041.8	c.281C>T	p.Ala94Val	missense_variant	5/8	5	NM_001037540.3	A2

Frequencies

GnomAD3 genomes AF: 0.00212 AC: 238 AN: 112106 Hom.: 2 Cov.: 24 AF XY: 0.00222 AC XY: 76 AN XY: 34292

Gnomad AFR AF: 0.000812

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00149

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00265

GnomAD3 exomes AF: 0.00380 AC: 660 AN: 173701 Hom.: 6 AF XY: 0.00208 AC XY: 124 AN XY: 59565

Gnomad AFR exome AF: 0.000464

Gnomad AMR exome AF: 0.0196

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00919

Gnomad SAS exome AF: 0.0000612

Gnomad FIN exome AF: 0.00133

Gnomad NFE exome AF: 0.0000882

Gnomad OTH exome AF: 0.00353

GnomAD4 exome AF: 0.00111 AC: 1170 AN: 1055775 Hom.: 6 Cov.: 23 AF XY: 0.000962 AC XY: 314 AN XY: 326393

Gnomad4 AFR exome AF: 0.000551

Gnomad4 AMR exome AF: 0.0199

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0101

Gnomad4 SAS exome AF: 0.0000390

Gnomad4 FIN exome AF: 0.00191

Gnomad4 NFE exome AF: 0.0000421

Gnomad4 OTH exome AF: 0.00157

GnomAD4 genome AF: 0.00214 AC: 240 AN: 112157 Hom.: 2 Cov.: 24 AF XY: 0.00227 AC XY: 78 AN XY: 34353

Gnomad4 AFR AF: 0.000811

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00804

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00149

Gnomad4 NFE AF: 0.000113

Gnomad4 OTH AF: 0.00262

Alfa AF: 0.000758 Hom.: 22

Bravo AF: 0.00311

ESP6500AA AF: 0.000782 AC: 3

ESP6500EA AF: 0.000446 AC: 3

ExAC AF: 0.00288 AC: 350

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.0010
Dann	Benign	0.67
DEOGEN2	Benign	0.012	T;.;.
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.57	T;T;T
MetaRNN	Benign	0.0051	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.37	N;N;N
REVEL	Benign	0.017
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.31	B;B;.
Vest4		0.060
MVP		0.12
MPC		0.93
ClinPred		0.0050	T
GERP RS		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.031

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;