rs11195199

Positions:

chr10-110583833-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005445.4(SMC3):c.970-8G>A 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 0.115 in 1,608,740 control chromosomes in the GnomAD database, including 12,725 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1221 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11504 hom. )

Consequence

SMC3
NM_005445.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001165

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.25

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 10-110583833-G-A is Benign according to our data. Variant chr10-110583833-G-A is described in ClinVar as [Benign]. Clinvar id is 159992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-110583833-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMC3	NM_005445.4 linkuse as main transcript	c.970-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000361804.5	NP_005436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMC3	ENST00000361804.5 linkuse as main transcript	c.970-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005445.4	ENSP00000354720	P1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17725

AN:

151818

Hom.:

1217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0827

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.151

AC:

37473

AN:

248774

Hom.:

3330

AF XY:

0.148

AC XY:

19939

AN XY:

134944

show subpopulations

Gnomad AFR exome

AF:

0.0836

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.247

Gnomad SAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.109

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.115

AC:

167743

AN:

1456804

Hom.:

11504

Cov.:

AF XY:

0.117

AC XY:

84795

AN XY:

724704

show subpopulations

Gnomad4 AFR exome

AF:

0.0808

Gnomad4 AMR exome

AF:

0.248

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.298

Gnomad4 SAS exome

AF:

0.177

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.0980

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.117

AC:

17751

AN:

151936

Hom.:

1221

Cov.:

AF XY:

0.122

AC XY:

9055

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.0828

Gnomad4 AMR

AF:

0.175

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.263

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.107

Hom.:

992

Bravo

AF:

0.119

Asia WGS

AF:

0.213

AC:

740

AN:

3478

EpiCase

AF:

0.104

EpiControl

AF:

0.109

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 22, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -

Cornelia de Lange syndrome 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.0

DANN

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over