10-110567687-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000684988.1(SMC3):​n.4G>T variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00000105 in 948,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: SMC3 ENST00000684988.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000105 AC: 1 AN: 948896 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 487842

African (AFR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 69706

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3352

European-Non Finnish (NFE) AF: 0.00000150 AC: 1 AN: 668482

Other (OTH) AF: 0.00 AC: 0 AN: 42770

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Benign	0.97
PhyloP100		4.1
PromoterAI		-0.49	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;