chr10-110568767-CT-C

Position:

• chr10-110568767-CT-C

Variant summary

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

The NM_005445.4(SMC3):​c.16-158del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 142,948 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0086 (7 hom., cov: 27)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Likely 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-CT-C is Benign according to our data. Variant chr10-110568767-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1209217.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00865 (1236/142948) while in subpopulation SAS AF= 0.0189 (86/4542). AF 95% confidence interval is 0.0157. There are 7 homozygotes in gnomad4. There are 658 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1236 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00861 AC: 1230 AN: 142896 Hom.: 7 Cov.: 27

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.00598

Gnomad ASJ AF: 0.00478

Gnomad EAS AF: 0.00120

Gnomad SAS AF: 0.0184

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.00685

Gnomad NFE AF: 0.00590

Gnomad OTH AF: 0.00668

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

GnomAD4 genome AF: 0.00865 AC: 1236 AN: 142948 Hom.: 7 Cov.: 27 AF XY: 0.00948 AC XY: 658 AN XY: 69382

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.00598

Gnomad4 ASJ AF: 0.00478

Gnomad4 EAS AF: 0.00120

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.00590

Gnomad4 OTH AF: 0.00665

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 19, 2019

- -

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: rs35132779; hg19: chr10-112328525;