rs11195213

Variant names:

• chr10-110601178-A-G
• rs11195213
• NM_005445.4:c.2644+48A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-110601178-A-G
• chr10-110601178-A-C
• chr10-110601178-A-T

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.2644+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,295,924 control chromosomes in the GnomAD database, including 11,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1231 hom., cov: 32)
  • Exomes 𝑓: 0.13 (10575 hom.)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.942
• Publications: 5 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=-0.79).
• BP6: Variant 10-110601178-A-G is Benign according to our data. Variant chr10-110601178-A-G is described in ClinVar as Benign. ClinVar VariationId is 259769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 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.2644+48A>G		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.2644+48A>G		intron	N/A	ENSP00000354720.5	Q9UQE7
	SMC3	ENST00000918257.1		c.2668+48A>G		intron	N/A	ENSP00000588316.1
	SMC3	ENST00000966376.1		c.2662+48A>G		intron	N/A	ENSP00000636435.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17870 AN: 152126 Hom.: 1227 Cov.: 32

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.131

GnomAD2 exomes AF: 0.154 AC: 38178 AN: 247760 AF XY: 0.151

Gnomad AFR exome AF: 0.0830

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.247

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.126 AC: 143902 AN: 1143680 Hom.: 10575 Cov.: 16 AF XY: 0.128 AC XY: 74542 AN XY: 583958

African (AFR) AF: 0.0820 AC: 2228 AN: 27166

American (AMR) AF: 0.251 AC: 11104 AN: 44284

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3016 AN: 24128

East Asian (EAS) AF: 0.300 AC: 11480 AN: 38210

South Asian (SAS) AF: 0.187 AC: 14943 AN: 79974

European-Finnish (FIN) AF: 0.135 AC: 7140 AN: 52928

Middle Eastern (MID) AF: 0.172 AC: 881 AN: 5134

European-Non Finnish (NFE) AF: 0.106 AC: 86740 AN: 822168

Other (OTH) AF: 0.128 AC: 6370 AN: 49688

GnomAD4 genome AF: 0.118 AC: 17894 AN: 152244 Hom.: 1231 Cov.: 32 AF XY: 0.122 AC XY: 9118 AN XY: 74436

African (AFR) AF: 0.0816 AC: 3390 AN: 41564

American (AMR) AF: 0.175 AC: 2679 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1361 AN: 5182

South Asian (SAS) AF: 0.186 AC: 898 AN: 4828

European-Finnish (FIN) AF: 0.136 AC: 1440 AN: 10596

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7347 AN: 67998

Other (OTH) AF: 0.132 AC: 279 AN: 2112

Alfa AF: 0.0971 Hom.: 318

Bravo AF: 0.120

Asia WGS AF: 0.215 AC: 744 AN: 3472

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	-0.79
CADD	Benign	1.3
DANN	Benign	0.78
PhyloP100		0.94
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: rs11195213; hg19: chr10-112360936; COSMIC: COSV62418760;