rs559499419

Variant names:

• chr10-110567687-G-A
• rs559499419
• ENST00000684988.1:n.4G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-110567687-G-A
• chr10-110567687-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BS1 BS2

The ENST00000684988.1(SMC3):​n.4G>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.000437 in 1,101,270 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00048 (5 hom.)
• Consequence: SMC3 ENST00000684988.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.09
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BP6: Variant 10-110567687-G-A is Benign according to our data. Variant chr10-110567687-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 368882.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000197 (30/152378) while in subpopulation SAS AF = 0.00559 (27/4834). AF 95% confidence interval is 0.00394. There are 0 homozygotes in GnomAd4. There are 20 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High AC in GnomAd4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC3	NM_005445.4	c.-130G>A		upstream_gene_variant		ENST00000361804.5	NP_005436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMC3	ENST00000684988.1	n.4G>A		non_coding_transcript_exon_variant	Exon 1 of 25
SMC3	ENST00000691297.1	n.4G>A		non_coding_transcript_exon_variant	Exon 1 of 17
SMC3	ENST00000361804.5	c.-130G>A		upstream_gene_variant		1	NM_005445.4	ENSP00000354720.5
SMC3	ENST00000691527.1	n.-40G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152260 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000475 AC: 451 AN: 948892 Hom.: 5 Cov.: 12 AF XY: 0.000728 AC XY: 355 AN XY: 487840

African (AFR) AF: 0.0000869 AC: 2 AN: 23008

American (AMR) AF: 0.00 AC: 0 AN: 36308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20318

East Asian (EAS) AF: 0.00 AC: 0 AN: 35822

South Asian (SAS) AF: 0.00613 AC: 427 AN: 69704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49130

Middle Eastern (MID) AF: 0.000298 AC: 1 AN: 3352

European-Non Finnish (NFE) AF: 0.0000209 AC: 14 AN: 668480

Other (OTH) AF: 0.000164 AC: 7 AN: 42770

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152378 Hom.: 0 Cov.: 34 AF XY: 0.000268 AC XY: 20 AN XY: 74518

African (AFR) AF: 0.00 AC: 0 AN: 41598

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000604

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

De Lange syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.98
PhyloP100		4.1
PromoterAI		-0.46	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs559499419; hg19: chr10-112327445;