rs147070453

chr10-110589856-TTTAAAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005445.4(SMC3):c.1410-30_1410-25del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,592,840 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (5 hom.)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.73

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 10-110589856-TTTAAAA-T is Benign according to our data. Variant chr10-110589856-TTTAAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 259766.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00153 (233/152346) while in subpopulation AMR AF= 0.0034 (52/15296). AF 95% confidence interval is 0.00266. There are 0 homozygotes in gnomad4. There are 109 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 233 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC3	NM_005445.4	c.1410-30_1410-25del		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5	c.1410-30_1410-25del		intron_variant		1	NM_005445.4	P1

Frequencies

GnomAD3 genomes AF: 0.00153 AC: 233 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00166 AC: 415 AN: 250138 Hom.: 2 AF XY: 0.00162 AC XY: 219 AN XY: 135554

Gnomad AFR exome AF: 0.000444

Gnomad AMR exome AF: 0.000695

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.000325

Gnomad NFE exome AF: 0.00318

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00276 AC: 3978 AN: 1440494 Hom.: 5 AF XY: 0.00261 AC XY: 1871 AN XY: 718048

Gnomad4 AFR exome AF: 0.000453

Gnomad4 AMR exome AF: 0.000984

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000198

Gnomad4 FIN exome AF: 0.000825

Gnomad4 NFE exome AF: 0.00342

Gnomad4 OTH exome AF: 0.00208

GnomAD4 genome AF: 0.00153 AC: 233 AN: 152346 Hom.: 0 Cov.: 33 AF XY: 0.00146 AC XY: 109 AN XY: 74504

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00215

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00149 Hom.: 0

Bravo AF: 0.00188

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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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: rs147070453; hg19: chr10-112349614;