rs55750861

Variant names:

• chr10-110567920-C-CA
• rs55750861
• NM_005445.4:c.15+89_15+90insA

Your query was ambiguous. Multiple possible variants found:

• chr10-110567920-C-CA
• chr10-110567920-C-CG

Variant summary

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

The NM_005445.4(SMC3):​c.15+89_15+90insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 1,500,992 control chromosomes in the GnomAD database, including 617,965 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (53227 hom., cov: 0)
  • Exomes 𝑓: 0.91 (564738 hom.)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.26
• Publications: 2 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 10-110567920-C-CA is Benign according to our data. Variant chr10-110567920-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1261004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 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.15+89_15+90insA		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.15+89_15+90insA		intron	N/A	ENSP00000354720.5	Q9UQE7
	SMC3	ENST00000918257.1		c.15+89_15+90insA		intron	N/A	ENSP00000588316.1
	SMC3	ENST00000966376.1		c.15+89_15+90insA		intron	N/A	ENSP00000636435.1

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124947 AN: 152056 Hom.: 53225 Cov.: 0

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.913 AC: 1231325 AN: 1348818 Hom.: 564738 AF XY: 0.915 AC XY: 617749 AN XY: 675080

African (AFR) AF: 0.560 AC: 17421 AN: 31090

American (AMR) AF: 0.833 AC: 34823 AN: 41814

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 23144 AN: 25138

East Asian (EAS) AF: 0.956 AC: 36642 AN: 38324

South Asian (SAS) AF: 0.931 AC: 76877 AN: 82564

European-Finnish (FIN) AF: 0.951 AC: 48662 AN: 51144

Middle Eastern (MID) AF: 0.849 AC: 4662 AN: 5488

European-Non Finnish (NFE) AF: 0.923 AC: 938640 AN: 1016794

Other (OTH) AF: 0.894 AC: 50454 AN: 56462

GnomAD4 genome AF: 0.821 AC: 124981 AN: 152174 Hom.: 53227 Cov.: 0 AF XY: 0.826 AC XY: 61431 AN XY: 74394

African (AFR) AF: 0.571 AC: 23676 AN: 41498

American (AMR) AF: 0.831 AC: 12725 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3208 AN: 3472

East Asian (EAS) AF: 0.964 AC: 4946 AN: 5130

South Asian (SAS) AF: 0.931 AC: 4500 AN: 4832

European-Finnish (FIN) AF: 0.958 AC: 10180 AN: 10622

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.926 AC: 62958 AN: 67998

Other (OTH) AF: 0.819 AC: 1732 AN: 2116

Alfa AF: 0.850 Hom.: 2891

Bravo AF: 0.799

Asia WGS AF: 0.911 AC: 3167 AN: 3478

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		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs55750861; hg19: chr10-112327678; COSMIC: COSV62420209; COSMIC: COSV62420209;