Variant rs11195200 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005445.4(SMC3):c.1092-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,609,840 control chromosomes in the GnomAD database, including 12,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1221 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11583 hom. )

Consequence

SMC3
NM_005445.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.18

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=-0.86).

BP6

Variant 10-110584165-T-C is Benign according to our data. Variant chr10-110584165-T-C is described in ClinVar as [Benign]. Clinvar id is 259765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-110584165-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC3	NM_005445.4 linkuse as main transcript	c.1092-18T>C		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5 linkuse as main transcript	c.1092-18T>C		intron_variant		1	NM_005445.4	P1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17735

AN:

152142

Hom.:

1217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0826

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.151

AC:

38019

AN:

250984

Hom.:

3396

AF XY:

0.149

AC XY:

20205

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.0842

Gnomad AMR exome

AF:

0.263

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.247

Gnomad SAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.116

AC:

168400

AN:

1457580

Hom.:

11583

Cov.:

AF XY:

0.117

AC XY:

85145

AN XY:

725386

show subpopulations

Gnomad4 AFR exome

AF:

0.0810

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.297

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.0982

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.117

AC:

17761

AN:

152260

Hom.:

1221

Cov.:

AF XY:

0.122

AC XY:

9052

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0827

Gnomad4 AMR

AF:

0.175

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.262

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.111

Hom.:

337

Bravo

AF:

0.119

Asia WGS

AF:

0.214

AC:

741

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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	-	- -

Cornelia de Lange syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

DANN

Benign

0.43

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

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