rs7911129

Variant names:

• chr10-110581113-A-G
• rs7911129
• NM_005445.4:c.547+92A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-110581113-A-G
• chr10-110581113-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.547+92A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 775,298 control chromosomes in the GnomAD database, including 4,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2350 hom., cov: 32)
  • Exomes 𝑓: 0.054 (1745 hom.)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.517
• Publications: 3 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=-0.9).
• BP6: Variant 10-110581113-A-G is Benign according to our data. Variant chr10-110581113-A-G is described in ClinVar as Benign. ClinVar VariationId is 1287430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 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.547+92A>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.547+92A>G		intron	N/A	ENSP00000354720.5	Q9UQE7
	SMC3	ENST00000918257.1		c.547+92A>G		intron	N/A	ENSP00000588316.1
	SMC3	ENST00000966376.1		c.565+92A>G		intron	N/A	ENSP00000636435.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18567 AN: 151992 Hom.: 2336 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0673

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0437

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0449

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.0536 AC: 33407 AN: 623192 Hom.: 1745 AF XY: 0.0518 AC XY: 17598 AN XY: 339802

African (AFR) AF: 0.326 AC: 5771 AN: 17716

American (AMR) AF: 0.0466 AC: 2002 AN: 42944

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 878 AN: 20842

East Asian (EAS) AF: 0.000169 AC: 6 AN: 35492

South Asian (SAS) AF: 0.0456 AC: 3150 AN: 69032

European-Finnish (FIN) AF: 0.0498 AC: 2218 AN: 44522

Middle Eastern (MID) AF: 0.100 AC: 411 AN: 4112

European-Non Finnish (NFE) AF: 0.0469 AC: 16690 AN: 355552

Other (OTH) AF: 0.0692 AC: 2281 AN: 32980

GnomAD4 genome AF: 0.122 AC: 18627 AN: 152106 Hom.: 2350 Cov.: 32 AF XY: 0.119 AC XY: 8848 AN XY: 74364

African (AFR) AF: 0.322 AC: 13349 AN: 41446

American (AMR) AF: 0.0671 AC: 1026 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0439 AC: 212 AN: 4828

European-Finnish (FIN) AF: 0.0504 AC: 533 AN: 10580

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0448 AC: 3049 AN: 67996

Other (OTH) AF: 0.115 AC: 243 AN: 2112

Alfa AF: 0.0933 Hom.: 308

Bravo AF: 0.134

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.61
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: rs7911129; hg19: chr10-112340871;