dbSNP rs55750861: SMC3:c.15+89_15+90insA (chr10-110567920-C-CA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_005445.4(SMC3):c.15+89_15+90insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 1,500,992 control chromosomes in the GnomAD database, including 617,965 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.82 ( 53227 hom., cov: 0)

Exomes 𝑓: 0.91 ( 564738 hom. )

Consequence

SMC3
NM_005445.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.26

Publications

2 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 -10 ACMG points.

BP6

Variant 10-110567920-C-CA is Benign according to our data. Variant chr10-110567920-C-CA is described in ClinVar as [Benign]. Clinvar id is 1261004.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC3	NM_005445.4 link	c.15+89_15+90insA		intron_variant	Intron 1 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.15+89_15+90insA		intron_variant	Intron 1 of 28	1	NM_005445.4	ENSP00000354720.5		Q9UQE7

Frequencies

GnomAD3 genomes

AF:

0.822

AC:

124947

AN:

152056

Hom.:

53225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.571

Gnomad AMI

AF:

0.887

Gnomad AMR

AF:

0.832

Gnomad ASJ

AF:

0.924

Gnomad EAS

AF:

0.964

Gnomad SAS

AF:

0.931

Gnomad FIN

AF:

0.958

Gnomad MID

AF:

0.864

Gnomad NFE

AF:

0.926

Gnomad OTH

AF:

0.817

GnomAD4 exome

AF:

0.913

AC:

1231325

AN:

1348818

Hom.:

564738

AF XY:

0.915

AC XY:

617749

AN XY:

675080

show subpopulations

African (AFR)

AF:

0.560

AC:

17421

AN:

31090

American (AMR)

AF:

0.833

AC:

34823

AN:

41814

Ashkenazi Jewish (ASJ)

AF:

0.921

AC:

23144

AN:

25138

East Asian (EAS)

AF:

0.956

AC:

36642

AN:

38324

South Asian (SAS)

AF:

0.931

AC:

76877

AN:

82564

European-Finnish (FIN)

AF:

0.951

AC:

48662

AN:

51144

Middle Eastern (MID)

AF:

0.849

AC:

4662

AN:

5488

European-Non Finnish (NFE)

AF:

0.923

AC:

938640

AN:

1016794

Other (OTH)

AF:

0.894

AC:

50454

AN:

56462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

5227

10455

15682

20910

26137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.821

AC:

124981

AN:

152174

Hom.:

53227

Cov.:

AF XY:

0.826

AC XY:

61431

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.571

AC:

23676

AN:

41498

American (AMR)

AF:

0.831

AC:

12725

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.924

AC:

3208

AN:

3472

East Asian (EAS)

AF:

0.964

AC:

4946

AN:

5130

South Asian (SAS)

AF:

0.931

AC:

4500

AN:

4832

European-Finnish (FIN)

AF:

0.958

AC:

10180

AN:

10622

Middle Eastern (MID)

AF:

0.854

AC:

251

AN:

294

European-Non Finnish (NFE)

AF:

0.926

AC:

62958

AN:

67998

Other (OTH)

AF:

0.819

AC:

1732

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

990

1981

2971

3962

4952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.850

Hom.:

2891

Bravo

AF:

0.799

Asia WGS

AF:

0.911

AC:

3167

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.3

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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rs55750861

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