chr10-110569234-CTAGG-C

Position:

• chr10-110569234-CTAGG-C

Variant summary

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

The NM_005445.4(SMC3):​c.91+225_91+228del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,082 control chromosomes in the GnomAD database, including 1,824 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1824 hom., cov: 30)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.353

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 10-110569234-CTAGG-C is Benign according to our data. Variant chr10-110569234-CTAGG-C is described in ClinVar as [Benign]. Clinvar id is 1262777.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC3	NM_005445.4	c.91+225_91+228del		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5	c.91+225_91+228del		intron_variant		1	NM_005445.4	P1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16798 AN: 151964 Hom.: 1813 Cov.: 30

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0442

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0412

Gnomad FIN AF: 0.0506

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.111 AC: 16851 AN: 152082 Hom.: 1824 Cov.: 30 AF XY: 0.108 AC XY: 8034 AN XY: 74352

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.0623

Gnomad4 ASJ AF: 0.0442

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0414

Gnomad4 FIN AF: 0.0506

Gnomad4 NFE AF: 0.0446

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0836 Hom.: 164

Bravo AF: 0.120

Asia WGS AF: 0.0430 AC: 150 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

Nov 22, 2018

- -

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: rs111940010; hg19: chr10-112328992;