chr10-110568859-AAAAC-A

Position:

• chr10-110568859-AAAAC-A

Variant summary

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

The NM_005445.4(SMC3):​c.16-76_16-73del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 872,546 control chromosomes in the GnomAD database, including 3,931 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1863 hom., cov: 30)
  • Exomes 𝑓: 0.062 (2068 hom.)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.92

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 -10 ACMG points.

• BP6: Variant 10-110568859-AAAAC-A is Benign according to our data. Variant chr10-110568859-AAAAC-A is described in ClinVar as [Benign]. Clinvar id is 1246522.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC3	NM_005445.4	c.16-76_16-73del		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5	c.16-76_16-73del		intron_variant		1	NM_005445.4	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18076 AN: 151862 Hom.: 1851 Cov.: 30

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.0618 AC: 44519 AN: 720566 Hom.: 2068 AF XY: 0.0590 AC XY: 22723 AN XY: 384898

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0425

Gnomad4 EAS exome AF: 0.0415

Gnomad4 SAS exome AF: 0.0474

Gnomad4 FIN exome AF: 0.0591

Gnomad4 NFE exome AF: 0.0518

Gnomad4 OTH exome AF: 0.0768

GnomAD4 genome AF: 0.119 AC: 18132 AN: 151980 Hom.: 1863 Cov.: 30 AF XY: 0.118 AC XY: 8734 AN XY: 74302

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0455

Gnomad4 EAS AF: 0.0329

Gnomad4 SAS AF: 0.0478

Gnomad4 FIN AF: 0.0603

Gnomad4 NFE AF: 0.0508

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0922 Hom.: 143

Bravo AF: 0.131

Asia WGS AF: 0.0660 AC: 231 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

Dec 05, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs147510961; hg19: chr10-112328617;