10-110568767-C-CTTT

Variant summary

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

The NM_005445.4(SMC3):c.16-160_16-158dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 143,158 control chromosomes in the GnomAD database, including 208 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.032 (208 hom., cov: 27)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.208

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 10-110568767-C-CTTT is Benign according to our data. Variant chr10-110568767-C-CTTT is described in ClinVar as [Benign]. Clinvar id is 1180142.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC3	NM_005445.4	c.16-160_16-158dup		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5	c.16-160_16-158dup		intron_variant		1	NM_005445.4	P1

Frequencies

GnomAD3 genomes AF: 0.0323 AC: 4629 AN: 143106 Hom.: 204 Cov.: 27

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.00388

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00219

Gnomad FIN AF: 0.000117

Gnomad MID AF: 0.0170

Gnomad NFE AF: 0.00552

Gnomad OTH AF: 0.0313

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0324 AC: 4645 AN: 143158 Hom.: 208 Cov.: 27 AF XY: 0.0311 AC XY: 2165 AN XY: 69532

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0151

Gnomad4 ASJ AF: 0.00388

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00176

Gnomad4 FIN AF: 0.000117

Gnomad4 NFE AF: 0.00552

Gnomad4 OTH AF: 0.0311

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

May 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35132779; hg19: chr10-112328525;