rs94499

chr11-134153833-A-Gchr11-134153833-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015261.3(NCAPD3):c.4253-470T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 186,584 control chromosomes in the GnomAD database, including 5,499 homozygotes. 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: 𝑓 0.24 (4677 hom., cov: 32)
  • Exomes 𝑓: 0.20 (822 hom.)
• Consequence: NCAPD3 NM_015261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643

Genes affected

NCAPD3 (HGNC:28952): (non-SMC condensin II complex subunit D3) Condensin complexes I and II play essential roles in mitotic chromosome assembly and segregation. Both condensins contain 2 invariant structural maintenance of chromosome (SMC) subunits, SMC2 (MIM 605576) and SMC4 (MIM 605575), but they contain different sets of non-SMC subunits. NCAPD3 is 1 of 3 non-SMC subunits that define condensin II (Ono et al., 2003 [PubMed 14532007]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAPD3	NM_015261.3	c.4253-470T>C		intron_variant		ENST00000534548.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAPD3	ENST00000534548.7	c.4253-470T>C		intron_variant		1	NM_015261.3	P2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37146 AN: 151900 Hom.: 4670 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.198 AC: 6845 AN: 34566 Hom.: 822 Cov.: 0 AF XY: 0.198 AC XY: 3546 AN XY: 17906

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.245 AC: 37182 AN: 152018 Hom.: 4677 Cov.: 32 AF XY: 0.245 AC XY: 18223 AN XY: 74294

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.249

Alfa AF: 0.110 Hom.: 149

Bravo AF: 0.238

Asia WGS AF: 0.265 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.46
Dann	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs94499; hg19: chr11-134023728;