rs7914351

Variant names:

• chr10-110577944-T-G
• rs7914351
• NM_005445.4:c.350+30T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-110577944-T-G
• chr10-110577944-T-A
• chr10-110577944-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+30T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,441,184 control chromosomes in the GnomAD database, including 4,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1869 hom., cov: 32)
  • Exomes 𝑓: 0.053 (2918 hom.)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.952
• Publications: 4 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=-0.82).
• BP6: Variant 10-110577944-T-G is Benign according to our data. Variant chr10-110577944-T-G is described in ClinVar as Benign. ClinVar VariationId is 1285681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 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+30T>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.350+30T>G		intron	N/A	ENSP00000354720.5	Q9UQE7
	SMC3	ENST00000918257.1		c.350+30T>G		intron	N/A	ENSP00000588316.1
	SMC3	ENST00000966376.1		c.368+30T>G		intron	N/A	ENSP00000636435.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16928 AN: 151948 Hom.: 1858 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.0507

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.0578 AC: 14358 AN: 248366 AF XY: 0.0544

Gnomad AFR exome AF: 0.287

Gnomad AMR exome AF: 0.0408

Gnomad ASJ exome AF: 0.0425

Gnomad EAS exome AF: 0.000439

Gnomad FIN exome AF: 0.0484

Gnomad NFE exome AF: 0.0469

Gnomad OTH exome AF: 0.0590

GnomAD4 exome AF: 0.0525 AC: 67708 AN: 1289118 Hom.: 2918 Cov.: 20 AF XY: 0.0516 AC XY: 33574 AN XY: 650592

African (AFR) AF: 0.298 AC: 9079 AN: 30480

American (AMR) AF: 0.0440 AC: 1954 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.0416 AC: 1041 AN: 25044

East Asian (EAS) AF: 0.000155 AC: 6 AN: 38790

South Asian (SAS) AF: 0.0450 AC: 3716 AN: 82608

European-Finnish (FIN) AF: 0.0485 AC: 2552 AN: 52652

Middle Eastern (MID) AF: 0.0981 AC: 532 AN: 5424

European-Non Finnish (NFE) AF: 0.0475 AC: 45333 AN: 955162

Other (OTH) AF: 0.0641 AC: 3495 AN: 54504

GnomAD4 genome AF: 0.112 AC: 16983 AN: 152066 Hom.: 1869 Cov.: 32 AF XY: 0.109 AC XY: 8096 AN XY: 74370

African (AFR) AF: 0.285 AC: 11795 AN: 41370

American (AMR) AF: 0.0630 AC: 963 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 155 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0437 AC: 211 AN: 4828

European-Finnish (FIN) AF: 0.0507 AC: 538 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0447 AC: 3042 AN: 68000

Other (OTH) AF: 0.104 AC: 219 AN: 2114

Alfa AF: 0.0401 Hom.: 61

Bravo AF: 0.121

Asia WGS AF: 0.0440 AC: 154 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	-0.82
CADD	Benign	4.6
DANN	Benign	0.32
PhyloP100		0.95
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: rs7914351; hg19: chr10-112337702;