10-110568767-C-CTTT

Variant names:

• chr10-110568767-C-CTTT
• rs35132779
• NM_005445.4:c.16-160_16-158dupTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005445.4(SMC3):​c.16-160_16-158dupTTT 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
• Publications: 0 publications found

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]

SMC3 Gene-Disease associations (from GenCC):

• Cornelia de Lange syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Cornelia de Lange syndrome 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMC3	NM_005445.4	c.16-160_16-158dupTTT		intron_variant	Intron 1 of 28	ENST00000361804.5	NP_005436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMC3	ENST00000361804.5	c.16-171_16-170insTTT		intron_variant	Intron 1 of 28	1	NM_005445.4	ENSP00000354720.5

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

African (AFR) AF: 0.102 AC: 3981 AN: 39130

American (AMR) AF: 0.0151 AC: 217 AN: 14408

Ashkenazi Jewish (ASJ) AF: 0.00388 AC: 13 AN: 3348

East Asian (EAS) AF: 0.00 AC: 0 AN: 5004

South Asian (SAS) AF: 0.00176 AC: 8 AN: 4544

European-Finnish (FIN) AF: 0.000117 AC: 1 AN: 8538

Middle Eastern (MID) AF: 0.0182 AC: 5 AN: 274

European-Non Finnish (NFE) AF: 0.00552 AC: 359 AN: 65054

Other (OTH) AF: 0.0311 AC: 61 AN: 1960

Alfa AF: 0.000563 Hom.: 57

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 25, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs35132779; hg19: chr10-112328525;