Variant 10-110568892-A-AT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_005445.4(SMC3):c.16-38dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 1,103,746 control chromosomes in the GnomAD database, including 4,252 homozygotes. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.12 ( 1873 hom., cov: 30)

Exomes 𝑓: 0.057 ( 2379 hom. )

Consequence

SMC3
NM_005445.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.376

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 10-110568892-A-AT is Benign according to our data. Variant chr10-110568892-A-AT is described in ClinVar as [Benign]. Clinvar id is 1233049.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC3	NM_005445.4 linkuse as main transcript	c.16-38dup		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5 linkuse as main transcript	c.16-38dup		intron_variant		1	NM_005445.4	P1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18059

AN:

151678

Hom.:

1861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.0453

Gnomad EAS

AF:

0.0336

Gnomad SAS

AF:

0.0476

Gnomad FIN

AF:

0.0612

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0510

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.0608

AC:

14322

AN:

235420

Hom.:

688

AF XY:

0.0558

AC XY:

7130

AN XY:

127840

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.0882

Gnomad ASJ exome

AF:

0.0384

Gnomad EAS exome

AF:

0.0246

Gnomad SAS exome

AF:

0.0368

Gnomad FIN exome

AF:

0.0538

Gnomad NFE exome

AF:

0.0457

Gnomad OTH exome

AF:

0.0585

GnomAD4 exome

AF:

0.0570

AC:

54240

AN:

951952

Hom.:

2379

Cov.:

AF XY:

0.0554

AC XY:

27496

AN XY:

496070

show subpopulations

Gnomad4 AFR exome

AF:

0.273

Gnomad4 AMR exome

AF:

0.109

Gnomad4 ASJ exome

AF:

0.0419

Gnomad4 EAS exome

AF:

0.0408

Gnomad4 SAS exome

AF:

0.0464

Gnomad4 FIN exome

AF:

0.0586

Gnomad4 NFE exome

AF:

0.0471

Gnomad4 OTH exome

AF:

0.0716

GnomAD4 genome

AF:

0.119

AC:

18115

AN:

151794

Hom.:

1873

Cov.:

AF XY:

0.118

AC XY:

8726

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.278

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.0453

Gnomad4 EAS

AF:

0.0336

Gnomad4 SAS

AF:

0.0479

Gnomad4 FIN

AF:

0.0612

Gnomad4 NFE

AF:

0.0510

Gnomad4 OTH

AF:

0.119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

1.0

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

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