rs587784428

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005445.4(SMC3):​c.548-5_548-4dup variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 1,610,522 control chromosomes in the GnomAD database, including 1,987 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 349 hom., cov: 31)
Exomes 𝑓: 0.044 ( 1638 hom. )

Consequence

SMC3
NM_005445.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.55
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 10-110581915-C-CTT is Benign according to our data. Variant chr10-110581915-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 159989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMC3NM_005445.4 linkuse as main transcriptc.548-5_548-4dup splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000361804.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMC3ENST00000361804.5 linkuse as main transcriptc.548-5_548-4dup splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_005445.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0592
AC:
8995
AN:
152064
Hom.:
348
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.106
Gnomad AMI
AF:
0.0329
Gnomad AMR
AF:
0.0406
Gnomad ASJ
AF:
0.0435
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0363
Gnomad FIN
AF:
0.0503
Gnomad MID
AF:
0.0665
Gnomad NFE
AF:
0.0434
Gnomad OTH
AF:
0.0651
GnomAD3 exomes
AF:
0.0422
AC:
10565
AN:
250438
Hom.:
294
AF XY:
0.0424
AC XY:
5748
AN XY:
135682
show subpopulations
Gnomad AFR exome
AF:
0.105
Gnomad AMR exome
AF:
0.0273
Gnomad ASJ exome
AF:
0.0416
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.0361
Gnomad FIN exome
AF:
0.0480
Gnomad NFE exome
AF:
0.0449
Gnomad OTH exome
AF:
0.0502
GnomAD4 exome
AF:
0.0442
AC:
64512
AN:
1458340
Hom.:
1638
Cov.:
31
AF XY:
0.0440
AC XY:
31927
AN XY:
725718
show subpopulations
Gnomad4 AFR exome
AF:
0.109
Gnomad4 AMR exome
AF:
0.0295
Gnomad4 ASJ exome
AF:
0.0403
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0378
Gnomad4 FIN exome
AF:
0.0483
Gnomad4 NFE exome
AF:
0.0445
Gnomad4 OTH exome
AF:
0.0479
GnomAD4 genome
AF:
0.0592
AC:
9007
AN:
152182
Hom.:
349
Cov.:
31
AF XY:
0.0584
AC XY:
4343
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.106
Gnomad4 AMR
AF:
0.0406
Gnomad4 ASJ
AF:
0.0435
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0365
Gnomad4 FIN
AF:
0.0503
Gnomad4 NFE
AF:
0.0434
Gnomad4 OTH
AF:
0.0644
Alfa
AF:
0.0497
Hom.:
48
Bravo
AF:
0.0601
Asia WGS
AF:
0.0230
AC:
80
AN:
3476
EpiCase
AF:
0.0454
EpiControl
AF:
0.0445

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoFeb 08, 2013- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Dec 02, 2014- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:2
Likely benign, no assertion criteria providedclinical testingLaboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)-- -
Benign, criteria provided, single submitterclinical testingGeneDxOct 02, 2017- -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsApr 05, 2019This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Cornelia de Lange syndrome 3 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
De Lange syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199906378; hg19: chr10-112341673; API