Variant rs11380915 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.141

Variant links:

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]

SMC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
SMC3	NM_005445.4 linkuse as main transcript	c.724-6dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000361804.5	NP_005436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMC3	ENST00000361804.5 linkuse as main transcript	c.724-6dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005445.4	ENSP00000354720	P1

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

15237

AN:

151864

Hom.:

1385

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0483

AC XY:

34646

AN XY:

716932

show subpopulations

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.:

AF XY:

0.0979

AC XY:

7274

AN XY:

74326

show subpopulations

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.:

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

LINK: link

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

Labcorp Genetics (formerly Invitae), Labcorp

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

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over