rs11380915

chr10-110582548-G-GTchr10-110582548-G-GTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005445.4(SMC3):c.724-6dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 1,590,282 control chromosomes in the GnomAD database, including 3,871 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1389 hom., cov: 30)
  • Exomes 𝑓: 0.049 (2482 hom.)
• Consequence: SMC3 NM_005445.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.141

Genes affected

SMC3 (HGNC:2468): (structural maintenance of chromosomes 3) This gene belongs to the SMC3 subfamily of SMC proteins. The encoded protein occurs in certain cell types as either an intracellular, nuclear protein or a secreted protein. The nuclear form, known as structural maintenance of chromosomes 3, is a component of the multimeric cohesin complex that holds together sister chromatids during mitosis, enabling proper chromosome segregation. Post-translational modification of the encoded protein by the addition of chondroitin sulfate chains gives rise to the secreted proteoglycan bamacan, an abundant basement membrane protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 10-110582548-G-GT is Benign according to our data. Variant chr10-110582548-G-GT is described in ClinVar as [Benign]. Clinvar id is 159991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC3	NM_005445.4	c.724-6dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5	c.724-6dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005445.4	P1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15237 AN: 151864 Hom.: 1385 Cov.: 30

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0598

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0361

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0446

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.0541 AC: 13285 AN: 245618 Hom.: 653 AF XY: 0.0512 AC XY: 6813 AN XY: 132978

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.0385

Gnomad ASJ exome AF: 0.0420

Gnomad EAS exome AF: 0.000446

Gnomad SAS exome AF: 0.0363

Gnomad FIN exome AF: 0.0479

Gnomad NFE exome AF: 0.0469

Gnomad OTH exome AF: 0.0595

GnomAD4 exome AF: 0.0491 AC: 70654 AN: 1438300 Hom.: 2482 Cov.: 28 AF XY: 0.0483 AC XY: 34646 AN XY: 716932

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.0414

Gnomad4 ASJ exome AF: 0.0405

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.0381

Gnomad4 FIN exome AF: 0.0482

Gnomad4 NFE exome AF: 0.0455

Gnomad4 OTH exome AF: 0.0587

GnomAD4 genome AF: 0.100 AC: 15266 AN: 151982 Hom.: 1389 Cov.: 30 AF XY: 0.0979 AC XY: 7274 AN XY: 74326

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.0597

Gnomad4 ASJ AF: 0.0447

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0364

Gnomad4 FIN AF: 0.0503

Gnomad4 NFE AF: 0.0446

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0311 Hom.: 21

Bravo AF: 0.108

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 26, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 02, 2017

- -

Cornelia de Lange syndrome 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

De Lange syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11380915; hg19: chr10-112342306;