rs7911129

chr10-110581113-A-Gchr10-110581113-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.517

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1287430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC3	NM_005445.4	c.547+92A>G		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5	c.547+92A>G		intron_variant		1	NM_005445.4	P1

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

Gnomad4 AFR exome AF: 0.326

Gnomad4 AMR exome AF: 0.0466

Gnomad4 ASJ exome AF: 0.0421

Gnomad4 EAS exome AF: 0.000169

Gnomad4 SAS exome AF: 0.0456

Gnomad4 FIN exome AF: 0.0498

Gnomad4 NFE exome AF: 0.0469

Gnomad4 OTH exome AF: 0.0692

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

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.0671

Gnomad4 ASJ AF: 0.0447

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.0504

Gnomad4 NFE AF: 0.0448

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0872 Hom.: 264

Bravo AF: 0.134

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.0
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs7911129; hg19: chr10-112340871;