10-110582548-GT-GTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005445.4(SMC3):c.724-6dupT variant causes a splice region, 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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_region, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.141

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Cornelia de Lange syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Cornelia de Lange syndrome 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

SMC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMC3	NM_005445.4 link	c.724-6dupT		splice_region_variant, intron_variant	Intron 9 of 28	ENST00000361804.5	NP_005436.1	Q9UQE7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMC3	ENST00000361804.5 link	c.724-14_724-13insT		intron_variant	Intron 9 of 28	1	NM_005445.4	ENSP00000354720.5		Q9UQE7

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

GnomAD2 exomes

AF:

0.0541

AC:

13285

AN:

245618

AF XY:

0.0512

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 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

African (AFR)

AF:

0.251

AC:

8207

AN:

32754

American (AMR)

AF:

0.0414

AC:

1843

AN:

44566

Ashkenazi Jewish (ASJ)

AF:

0.0405

AC:

1054

AN:

26010

East Asian (EAS)

AF:

0.000177

AC:

AN:

39486

South Asian (SAS)

AF:

0.0381

AC:

3259

AN:

85470

European-Finnish (FIN)

AF:

0.0482

AC:

2568

AN:

53298

Middle Eastern (MID)

AF:

0.0931

AC:

529

AN:

5680

European-Non Finnish (NFE)

AF:

0.0455

AC:

49692

AN:

1091472

Other (OTH)

AF:

0.0587

AC:

3495

AN:

59564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

2753

5507

8260

11014

13767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.100

AC:

15266

AN:

151982

Hom.:

1389

Cov.:

AF XY:

0.0979

AC XY:

7274

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.246

AC:

10190

AN:

41416

American (AMR)

AF:

0.0597

AC:

912

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0447

AC:

155

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0364

AC:

175

AN:

4812

European-Finnish (FIN)

AF:

0.0503

AC:

532

AN:

10578

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0446

AC:

3029

AN:

67946

Other (OTH)

AF:

0.102

AC:

215

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

632

1264

1897

2529

3161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Mar 26, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Oct 02, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cornelia de Lange syndrome 3

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

De Lange syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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10-110582548-GT-GTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over