10-110567920-C-CA

Position:

• chr10-110567920-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005445.4(SMC3):​c.15+89_15+90insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 1,500,992 control chromosomes in the GnomAD database, including 617,965 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (53227 hom., cov: 0)
  • Exomes 𝑓: 0.91 (564738 hom.)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.26

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-110567920-C-CA is Benign according to our data. Variant chr10-110567920-C-CA is described in ClinVar as [Benign]. Clinvar id is 1261004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMC3	NM_005445.4	c.15+89_15+90insA		intron_variant		ENST00000361804.5	NP_005436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMC3	ENST00000361804.5	c.15+89_15+90insA		intron_variant		1	NM_005445.4	ENSP00000354720.5

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124947 AN: 152056 Hom.: 53225 Cov.: 0

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.913 AC: 1231325 AN: 1348818 Hom.: 564738 AF XY: 0.915 AC XY: 617749 AN XY: 675080

Gnomad4 AFR exome AF: 0.560

Gnomad4 AMR exome AF: 0.833

Gnomad4 ASJ exome AF: 0.921

Gnomad4 EAS exome AF: 0.956

Gnomad4 SAS exome AF: 0.931

Gnomad4 FIN exome AF: 0.951

Gnomad4 NFE exome AF: 0.923

Gnomad4 OTH exome AF: 0.894

GnomAD4 genome AF: 0.821 AC: 124981 AN: 152174 Hom.: 53227 Cov.: 0 AF XY: 0.826 AC XY: 61431 AN XY: 74394

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.831

Gnomad4 ASJ AF: 0.924

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.958

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.819

Alfa AF: 0.850 Hom.: 2891

Bravo AF: 0.799

Asia WGS AF: 0.911 AC: 3167 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs55750861; hg19: chr10-112327678; COSMIC: COSV62420209; COSMIC: COSV62420209;