Genetic Variant SMC3:c.16-76_16-73delACAA (chr10-110568859-AAAAC-A) – 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.16-76_16-73delACAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 872,546 control chromosomes in the GnomAD database, including 3,931 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1863 hom., cov: 30)

Exomes 𝑓: 0.062 ( 2068 hom. )

Consequence

SMC3
NM_005445.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.92

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 -10 ACMG points.

BP6

Variant 10-110568859-AAAAC-A is Benign according to our data. Variant chr10-110568859-AAAAC-A is described in ClinVar as [Benign]. Clinvar id is 1246522.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC3	NM_005445.4 link	c.16-76_16-73delACAA		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.16-78_16-75delAAAC		intron_variant	Intron 1 of 28	1	NM_005445.4	ENSP00000354720.5		Q9UQE7

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18076

AN:

151862

Hom.:

1851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0455

Gnomad EAS

AF:

0.0329

Gnomad SAS

AF:

0.0475

Gnomad FIN

AF:

0.0603

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0508

Gnomad OTH

AF:

0.120

GnomAD4 exome

AF:

0.0618

AC:

44519

AN:

720566

Hom.:

2068

AF XY:

0.0590

AC XY:

22723

AN XY:

384898

show subpopulations

African (AFR)

AF:

0.279

AC:

5292

AN:

18958

American (AMR)

AF:

0.109

AC:

4390

AN:

40138

Ashkenazi Jewish (ASJ)

AF:

0.0425

AC:

903

AN:

21232

East Asian (EAS)

AF:

0.0415

AC:

1485

AN:

35764

South Asian (SAS)

AF:

0.0474

AC:

3251

AN:

68610

European-Finnish (FIN)

AF:

0.0591

AC:

2903

AN:

49096

Middle Eastern (MID)

AF:

0.0978

AC:

412

AN:

4212

European-Non Finnish (NFE)

AF:

0.0518

AC:

23136

AN:

446810

Other (OTH)

AF:

0.0768

AC:

2747

AN:

35746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

2039

4078

6116

8155

10194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.119

AC:

18132

AN:

151980

Hom.:

1863

Cov.:

AF XY:

0.118

AC XY:

8734

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.279

AC:

11518

AN:

41346

American (AMR)

AF:

0.106

AC:

1622

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0455

AC:

158

AN:

3472

East Asian (EAS)

AF:

0.0329

AC:

171

AN:

5190

South Asian (SAS)

AF:

0.0478

AC:

230

AN:

4816

European-Finnish (FIN)

AF:

0.0603

AC:

637

AN:

10556

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0508

AC:

3454

AN:

68004

Other (OTH)

AF:

0.119

AC:

252

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

699

1398

2097

2796

3495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0922

Hom.:

143

Bravo

AF:

0.131

Asia WGS

AF:

0.0660

AC:

231

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 05, 2020

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

1.9

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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10-110568859-AAAAC-A

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