chr11-134160873-T-C

Variant names:

• chr11-134160873-T-C
• rs589670
• NM_015261.3:c.3685-799A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015261.3(NCAPD3):​c.3685-799A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,434 control chromosomes in the GnomAD database, including 17,976 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 0.45 (17976 hom., cov: 31)
• Consequence: NCAPD3 NM_015261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 1 publications found

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]

NCAPD3 Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• microcephaly 22, primary, autosomal recessive

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD3	NM_015261.3	c.3685-799A>G		intron_variant	Intron 28 of 34	ENST00000534548.7	NP_056076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAPD3	ENST00000534548.7	c.3685-799A>G		intron_variant	Intron 28 of 34	1	NM_015261.3	ENSP00000433681.3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 67953 AN: 151320 Hom.: 17936 Cov.: 31

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.412

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.449 AC: 68046 AN: 151434 Hom.: 17976 Cov.: 31 AF XY: 0.448 AC XY: 33135 AN XY: 73942

African (AFR) AF: 0.751 AC: 30961 AN: 41224

American (AMR) AF: 0.341 AC: 5182 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3466

East Asian (EAS) AF: 0.413 AC: 2109 AN: 5108

South Asian (SAS) AF: 0.287 AC: 1373 AN: 4778

European-Finnish (FIN) AF: 0.419 AC: 4371 AN: 10430

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21893 AN: 67910

Other (OTH) AF: 0.410 AC: 862 AN: 2104

Alfa AF: 0.413 Hom.: 1942

Bravo AF: 0.459

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.059
DANN	Benign	0.33
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs589670; hg19: chr11-134030768;