rs140102981

chr10-110573688-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005445.4(SMC3):c.92-19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,551,154 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (20 hom.)
• Consequence: SMC3 NM_005445.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0270

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 10-110573688-A-G is Benign according to our data. Variant chr10-110573688-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 259772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-110573688-A-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0029 (441/152288) while in subpopulation NFE AF= 0.00325 (221/68002). AF 95% confidence interval is 0.0029. There are 4 homozygotes in gnomad4. There are 259 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 440 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC3	NM_005445.4	c.92-19A>G		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5	c.92-19A>G		intron_variant		1	NM_005445.4	P1

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 440 AN: 152170 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00323

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00315 AC: 784 AN: 249262 Hom.: 5 AF XY: 0.00308 AC XY: 416 AN XY: 134884

Gnomad AFR exome AF: 0.000375

Gnomad AMR exome AF: 0.000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000166

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.00338

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00288 AC: 4035 AN: 1398866 Hom.: 20 Cov.: 25 AF XY: 0.00276 AC XY: 1933 AN XY: 699426

Gnomad4 AFR exome AF: 0.000497

Gnomad4 AMR exome AF: 0.000316

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000226

Gnomad4 FIN exome AF: 0.0146

Gnomad4 NFE exome AF: 0.00294

Gnomad4 OTH exome AF: 0.00172

GnomAD4 genome AF: 0.00290 AC: 441 AN: 152288 Hom.: 4 Cov.: 32 AF XY: 0.00348 AC XY: 259 AN XY: 74484

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0186

Gnomad4 NFE AF: 0.00325

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00230 Hom.: 0

Bravo AF: 0.00150

Asia WGS AF: 0.000579 AC: 2 AN: 3470

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 30, 2019

See Variant Classification Assertion Criteria. -

Cornelia de Lange syndrome 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.6
Dann	Benign	0.74

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: rs140102981; hg19: chr10-112333446;