rs11195200

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005445.4(SMC3):c.1092-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,609,840 control chromosomes in the GnomAD database, including 12,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1221 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11583 hom. )

Consequence

SMC3
NM_005445.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.18

Publications

8 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 10-110584165-T-C is Benign according to our data. Variant chr10-110584165-T-C is described in ClinVar as Benign. ClinVar VariationId is 259765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC3	NM_005445.4 link	c.1092-18T>C		intron_variant	Intron 12 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.1092-18T>C		intron_variant	Intron 12 of 28	1	NM_005445.4	ENSP00000354720.5		Q9UQE7

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17735

AN:

152142

Hom.:

1217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0826

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.130

GnomAD2 exomes

AF:

0.151

AC:

38019

AN:

250984

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.0842

Gnomad AMR exome

AF:

0.263

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.247

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.116

AC:

168400

AN:

1457580

Hom.:

11583

Cov.:

AF XY:

0.117

AC XY:

85145

AN XY:

725386

show subpopulations

African (AFR)

AF:

0.0810

AC:

2706

AN:

33402

American (AMR)

AF:

0.250

AC:

11170

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

3108

AN:

26094

East Asian (EAS)

AF:

0.297

AC:

11789

AN:

39644

South Asian (SAS)

AF:

0.179

AC:

15411

AN:

86164

European-Finnish (FIN)

AF:

0.134

AC:

7166

AN:

53416

Middle Eastern (MID)

AF:

0.163

AC:

939

AN:

5758

European-Non Finnish (NFE)

AF:

0.0982

AC:

108785

AN:

1108116

Other (OTH)

AF:

0.122

AC:

7326

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

7432

14864

22297

29729

37161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4074

8148

12222

16296

20370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.117

AC:

17761

AN:

152260

Hom.:

1221

Cov.:

AF XY:

0.122

AC XY:

9052

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0827

AC:

3435

AN:

41548

American (AMR)

AF:

0.175

AC:

2671

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

392

AN:

3472

East Asian (EAS)

AF:

0.262

AC:

1360

AN:

5182

South Asian (SAS)

AF:

0.179

AC:

865

AN:

4830

European-Finnish (FIN)

AF:

0.135

AC:

1430

AN:

10614

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7237

AN:

68014

Other (OTH)

AF:

0.131

AC:

277

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

802

1604

2406

3208

4010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.112

Hom.:

544

Bravo

AF:

0.119

Asia WGS

AF:

0.214

AC:

741

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 22, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Cornelia de Lange syndrome 3

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.43

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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