rs2275570

chr10-110581878-A-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.548-45A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,477,832 control chromosomes in the GnomAD database, including 12,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1215 hom., cov: 31)
  • Exomes 𝑓: 0.12 (11018 hom.)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.262

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=-0.82).
• BP6: Variant 10-110581878-A-C is Benign according to our data. Variant chr10-110581878-A-C is described in ClinVar as [Benign]. Clinvar id is 259771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC3	NM_005445.4	c.548-45A>C		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5	c.548-45A>C		intron_variant		1	NM_005445.4	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17722 AN: 152124 Hom.: 1211 Cov.: 31

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.152 AC: 37631 AN: 247788 Hom.: 3357 AF XY: 0.149 AC XY: 20047 AN XY: 134612

Gnomad AFR exome AF: 0.0839

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.248

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: 0.118 AC: 156213 AN: 1325590 Hom.: 11018 Cov.: 21 AF XY: 0.119 AC XY: 79775 AN XY: 667588

Gnomad4 AFR exome AF: 0.0813

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.298

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.0994

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.117 AC: 17748 AN: 152242 Hom.: 1215 Cov.: 31 AF XY: 0.121 AC XY: 9041 AN XY: 74426

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.131

Alfa AF: 0.117 Hom.: 213

Bravo AF: 0.119

Asia WGS AF: 0.214 AC: 741 AN: 3472

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

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	15
Dann	Benign	0.65

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: rs2275570; hg19: chr10-112341636; COSMIC: COSV62418751;