rs73210414

Positions:

• chrX-53394733-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_006306.4(SMC1A):​c.2973+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (10 hom., 408 hem., cov: 20)
  • Exomes 𝑓: 0.028 (616 hom. 3821 hem.)
  • Failed GnomAD Quality Control
• Consequence: SMC1A NM_006306.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.20

Genes affected

SMC1A (HGNC:11111): (structural maintenance of chromosomes 1A) Proper cohesion of sister chromatids is a prerequisite for the correct segregation of chromosomes during cell division. The cohesin multiprotein complex is required for sister chromatid cohesion. This complex is composed partly of two structural maintenance of chromosomes (SMC) proteins, SMC3 and either SMC1B or the protein encoded by this gene. Most of the cohesin complexes dissociate from the chromosomes before mitosis, although those complexes at the kinetochore remain. Therefore, the encoded protein is thought to be an important part of functional kinetochores. In addition, this protein interacts with BRCA1 and is phosphorylated by ATM, indicating a potential role for this protein in DNA repair. This gene, which belongs to the SMC gene family, is located in an area of the X-chromosome that escapes X inactivation. Mutations in this gene result in Cornelia de Lange syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-53394733-C-T is Benign according to our data. Variant chrX-53394733-C-T is described in ClinVar as [Benign]. Clinvar id is 259962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMC1A	NM_006306.4	c.2973+45G>A		intron_variant		ENST00000322213.9	NP_006297.2
SMC1A	NM_001281463.1	c.2907+45G>A		intron_variant			NP_001268392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMC1A	ENST00000322213.9	c.2973+45G>A		intron_variant		1	NM_006306.4	ENSP00000323421.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1417 AN: 105212 Hom.: 10 Cov.: 20 AF XY: 0.0146 AC XY: 408 AN XY: 27964 FAILED QC

Gnomad AFR AF: 0.00220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00620

Gnomad ASJ AF: 0.00235

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000441

Gnomad FIN AF: 0.0360

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0122

GnomAD3 exomes AF: 0.0200 AC: 2351 AN: 117285 Hom.: 154 AF XY: 0.0224 AC XY: 841 AN XY: 37555

Gnomad AFR exome AF: 0.00273

Gnomad AMR exome AF: 0.00671

Gnomad ASJ exome AF: 0.00496

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00106

Gnomad FIN exome AF: 0.0506

Gnomad NFE exome AF: 0.0343

Gnomad OTH exome AF: 0.0160

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0277 AC: 9574 AN: 345873 Hom.: 616 Cov.: 3 AF XY: 0.0364 AC XY: 3821 AN XY: 104947

Gnomad4 AFR exome AF: 0.00333

Gnomad4 AMR exome AF: 0.00756

Gnomad4 ASJ exome AF: 0.00645

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00127

Gnomad4 FIN exome AF: 0.0496

Gnomad4 NFE exome AF: 0.0375

Gnomad4 OTH exome AF: 0.0237

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0135 AC: 1417 AN: 105249 Hom.: 10 Cov.: 20 AF XY: 0.0146 AC XY: 408 AN XY: 28009

Gnomad4 AFR AF: 0.00219

Gnomad4 AMR AF: 0.00619

Gnomad4 ASJ AF: 0.00235

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000443

Gnomad4 FIN AF: 0.0360

Gnomad4 NFE AF: 0.0211

Gnomad4 OTH AF: 0.0120

Alfa AF: 0.0162 Hom.: 110

Bravo AF: 0.0105

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.41
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs73210414; hg19: chrX-53421653;