10-110568767-CTTTTT-CTTTTTTTT

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: PanelApp Australia, 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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005445.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC3	NM_005445.4	MANE Select	c.16-160_16-158dupTTT		intron	N/A	NP_005436.1	Q9UQE7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC3	ENST00000361804.5	TSL:1 MANE Select	c.16-171_16-170insTTT		intron	N/A	ENSP00000354720.5	Q9UQE7
	SMC3	ENST00000918257.1		c.16-171_16-170insTTT		intron	N/A	ENSP00000588316.1
	SMC3	ENST00000966376.1		c.16-171_16-170insTTT		intron	N/A	ENSP00000636435.1

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;