rs3737293

Positions:

• chr10-110589844-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005445.4(SMC3):​c.1410-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 1,556,270 control chromosomes in the GnomAD database, including 4,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (373 hom., cov: 33)
  • Exomes 𝑓: 0.074 (4280 hom.)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.780

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-110589844-T-C is Benign according to our data. Variant chr10-110589844-T-C is described in ClinVar as [Benign]. Clinvar id is 259767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC3	NM_005445.4	c.1410-48T>C		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5	c.1410-48T>C		intron_variant		1	NM_005445.4	P1

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9524 AN: 152184 Hom.: 369 Cov.: 33

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.0616

GnomAD3 exomes AF: 0.0694 AC: 17321 AN: 249638 Hom.: 713 AF XY: 0.0706 AC XY: 9558 AN XY: 135374

Gnomad AFR exome AF: 0.0295

Gnomad AMR exome AF: 0.0449

Gnomad ASJ exome AF: 0.0459

Gnomad EAS exome AF: 0.151

Gnomad SAS exome AF: 0.0793

Gnomad FIN exome AF: 0.0565

Gnomad NFE exome AF: 0.0713

Gnomad OTH exome AF: 0.0651

GnomAD4 exome AF: 0.0744 AC: 104419 AN: 1403968 Hom.: 4280 Cov.: 24 AF XY: 0.0749 AC XY: 52554 AN XY: 702036

Gnomad4 AFR exome AF: 0.0309

Gnomad4 AMR exome AF: 0.0470

Gnomad4 ASJ exome AF: 0.0452

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.0800

Gnomad4 FIN exome AF: 0.0567

Gnomad4 NFE exome AF: 0.0757

Gnomad4 OTH exome AF: 0.0751

GnomAD4 genome AF: 0.0626 AC: 9537 AN: 152302 Hom.: 373 Cov.: 33 AF XY: 0.0619 AC XY: 4608 AN XY: 74466

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.0569

Gnomad4 ASJ AF: 0.0496

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0877

Gnomad4 FIN AF: 0.0605

Gnomad4 NFE AF: 0.0759

Gnomad4 OTH AF: 0.0666

Alfa AF: 0.0695 Hom.: 478

Bravo AF: 0.0605

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.7
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs3737293; hg19: chr10-112349602; COSMIC: COSV62419034;