rs11195194

Variant names:

• chr10-110577935-T-A
• rs11195194
• NM_005445.4:c.350+21T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-110577935-T-A
• chr10-110577935-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005445.4(SMC3):​c.350+21T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,512,558 control chromosomes in the GnomAD database, including 12,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1246 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10938 hom.)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.524
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-110577935-T-A is Benign according to our data. Variant chr10-110577935-T-A is described in ClinVar as Benign. ClinVar VariationId is 259770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 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.350+21T>A		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.350+21T>A		intron	N/A	ENSP00000354720.5	Q9UQE7
	SMC3	ENST00000918257.1		c.350+21T>A		intron	N/A	ENSP00000588316.1
	SMC3	ENST00000966376.1		c.368+21T>A		intron	N/A	ENSP00000636435.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17886 AN: 151888 Hom.: 1242 Cov.: 32

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.130

GnomAD2 exomes AF: 0.152 AC: 37968 AN: 249312 AF XY: 0.150

Gnomad AFR exome AF: 0.0809

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.241

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.134

GnomAD4 exome AF: 0.114 AC: 155500 AN: 1360552 Hom.: 10938 Cov.: 23 AF XY: 0.116 AC XY: 79543 AN XY: 682800

African (AFR) AF: 0.0771 AC: 2447 AN: 31754

American (AMR) AF: 0.249 AC: 11087 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 3004 AN: 25484

East Asian (EAS) AF: 0.295 AC: 11502 AN: 39046

South Asian (SAS) AF: 0.178 AC: 14955 AN: 83936

European-Finnish (FIN) AF: 0.154 AC: 8128 AN: 52830

Middle Eastern (MID) AF: 0.161 AC: 899 AN: 5582

European-Non Finnish (NFE) AF: 0.0947 AC: 96670 AN: 1020508

Other (OTH) AF: 0.120 AC: 6808 AN: 56916

GnomAD4 genome AF: 0.118 AC: 17911 AN: 152006 Hom.: 1246 Cov.: 32 AF XY: 0.124 AC XY: 9202 AN XY: 74302

African (AFR) AF: 0.0809 AC: 3357 AN: 41474

American (AMR) AF: 0.174 AC: 2650 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3468

East Asian (EAS) AF: 0.257 AC: 1324 AN: 5150

South Asian (SAS) AF: 0.178 AC: 857 AN: 4806

European-Finnish (FIN) AF: 0.163 AC: 1719 AN: 10560

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7241 AN: 67972

Other (OTH) AF: 0.131 AC: 277 AN: 2112

Alfa AF: 0.0700 Hom.: 113

Bravo AF: 0.119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.92
DANN	Benign	0.71
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11195194; hg19: chr10-112337693; COSMIC: COSV62418744;