Variant rs11815960 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.805-26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,593,970 control chromosomes in the GnomAD database, including 3,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.092 ( 1103 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2347 hom. )

Consequence

SMC3
NM_005445.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.452

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

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-110583358-A-G is Benign according to our data. Variant chr10-110583358-A-G is described in ClinVar as [Benign]. Clinvar id is 1231960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 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.805-26A>G		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5 linkuse as main transcript	c.805-26A>G		intron_variant		1	NM_005445.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0914

AC:

13900

AN:

152066

Hom.:

1101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0547

Gnomad ASJ

AF:

0.0435

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0364

Gnomad FIN

AF:

0.0505

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0443

Gnomad OTH

AF:

0.0956

GnomAD3 exomes

AF:

0.0512

AC:

12756

AN:

249190

Hom.:

586

AF XY:

0.0491

AC XY:

6639

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.0357

Gnomad ASJ exome

AF:

0.0416

Gnomad EAS exome

AF:

0.000382

Gnomad SAS exome

AF:

0.0364

Gnomad FIN exome

AF:

0.0480

Gnomad NFE exome

AF:

0.0461

Gnomad OTH exome

AF:

0.0574

GnomAD4 exome

AF:

0.0478

AC:

68917

AN:

1441786

Hom.:

2347

Cov.:

AF XY:

0.0471

AC XY:

33876

AN XY:

718490

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.0387

Gnomad4 ASJ exome

AF:

0.0401

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0381

Gnomad4 FIN exome

AF:

0.0482

Gnomad4 NFE exome

AF:

0.0449

Gnomad4 OTH exome

AF:

0.0564

GnomAD4 genome

AF:

0.0915

AC:

13926

AN:

152184

Hom.:

1103

Cov.:

AF XY:

0.0895

AC XY:

6657

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.0546

Gnomad4 ASJ

AF:

0.0435

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0366

Gnomad4 FIN

AF:

0.0505

Gnomad4 NFE

AF:

0.0443

Gnomad4 OTH

AF:

0.0946

Alfa

AF:

0.0686

Hom.:

135

Bravo

AF:

0.0979

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.2

DANN

Benign

0.49

BranchPoint Hunter

1.0

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