rs7075340

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.2116+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,611,826 control chromosomes in the GnomAD database, including 784,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71443 hom., cov: 32)

Exomes 𝑓: 0.99 ( 713228 hom. )

Consequence

SMC3
NM_005445.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.00

Publications

6 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=-0.94).

BP6

Variant 10-110596573-G-A is Benign according to our data. Variant chr10-110596573-G-A is described in ClinVar as Benign. ClinVar VariationId is 259768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC3	NM_005445.4 link	c.2116+23G>A		intron_variant	Intron 19 of 28	ENST00000361804.5	NP_005436.1	Q9UQE7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMC3	ENST00000361804.5 link	c.2116+23G>A	intron_variant	Intron 19 of 28	1	NM_005445.4	ENSP00000354720.5	Q9UQE7
SMC3	ENST00000684988.1 link	n.2784G>A	non_coding_transcript_exon_variant	Exon 17 of 25
SMC3	ENST00000692792.1 link	n.2258G>A	non_coding_transcript_exon_variant	Exon 19 of 19

Frequencies

GnomAD3 genomes

AF:

0.968

AC:

147355

AN:

152188

Hom.:

71391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.924

Gnomad AMI

AF:

0.968

Gnomad AMR

AF:

0.949

Gnomad ASJ

AF:

0.989

Gnomad EAS

AF:

0.967

Gnomad SAS

AF:

0.995

Gnomad FIN

AF:

0.989

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.993

Gnomad OTH

AF:

0.965

GnomAD2 exomes

AF:

0.978

AC:

244304

AN:

249886

AF XY:

0.982

show subpopulations

Gnomad AFR exome

AF:

0.923

Gnomad AMR exome

AF:

0.927

Gnomad ASJ exome

AF:

0.988

Gnomad EAS exome

AF:

0.968

Gnomad FIN exome

AF:

0.989

Gnomad NFE exome

AF:

0.994

Gnomad OTH exome

AF:

0.981

GnomAD4 exome

AF:

0.988

AC:

1442670

AN:

1459520

Hom.:

713228

Cov.:

AF XY:

0.989

AC XY:

718430

AN XY:

726174

show subpopulations

African (AFR)

AF:

0.923

AC:

30836

AN:

33396

American (AMR)

AF:

0.928

AC:

41467

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.988

AC:

25785

AN:

26096

East Asian (EAS)

AF:

0.957

AC:

37931

AN:

39632

South Asian (SAS)

AF:

0.997

AC:

85837

AN:

86120

European-Finnish (FIN)

AF:

0.989

AC:

52641

AN:

53202

Middle Eastern (MID)

AF:

0.991

AC:

5706

AN:

5760

European-Non Finnish (NFE)

AF:

0.994

AC:

1103179

AN:

1110360

Other (OTH)

AF:

0.983

AC:

59288

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

741

1481

2222

2962

3703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21630

43260

64890

86520

108150

<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:

0.968

AC:

147465

AN:

152306

Hom.:

71443

Cov.:

AF XY:

0.968

AC XY:

72129

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.924

AC:

38403

AN:

41540

American (AMR)

AF:

0.949

AC:

14521

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.989

AC:

3431

AN:

3468

East Asian (EAS)

AF:

0.967

AC:

5009

AN:

5180

South Asian (SAS)

AF:

0.995

AC:

4803

AN:

4828

European-Finnish (FIN)

AF:

0.989

AC:

10502

AN:

10620

Middle Eastern (MID)

AF:

0.983

AC:

289

AN:

294

European-Non Finnish (NFE)

AF:

0.993

AC:

67581

AN:

68044

Other (OTH)

AF:

0.966

AC:

2043

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

252

504

757

1009

1261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.982

Hom.:

93009

Bravo

AF:

0.962

Asia WGS

AF:

0.973

AC:

3385

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 16, 2018

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 specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cornelia de Lange syndrome 3

Benign:1

Jul 15, 2021

Genome-Nilou Lab

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

-0.94

CADD

Benign

0.28

(source)

DANN

Benign

0.61

PhyloP100

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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