rs632951

Variant names:

• chr11-134164410-T-C
• rs632951
• NM_015261.3:c.3574-2519A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-134164410-T-C
• chr11-134164410-T-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.3574-2519A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,030 control chromosomes in the GnomAD database, including 18,144 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 (18144 hom., cov: 33)
• Consequence: NCAPD3 NM_015261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD3	NM_015261.3	c.3574-2519A>G		intron_variant	Intron 27 of 34	ENST00000534548.7	NP_056076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAPD3	ENST00000534548.7	c.3574-2519A>G		intron_variant	Intron 27 of 34	1	NM_015261.3	ENSP00000433681.3

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68425 AN: 151912 Hom.: 18104 Cov.: 33

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.451 AC: 68519 AN: 152030 Hom.: 18144 Cov.: 33 AF XY: 0.450 AC XY: 33407 AN XY: 74304

African (AFR) AF: 0.752 AC: 31217 AN: 41496

American (AMR) AF: 0.342 AC: 5225 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3464

East Asian (EAS) AF: 0.414 AC: 2138 AN: 5160

South Asian (SAS) AF: 0.291 AC: 1400 AN: 4814

European-Finnish (FIN) AF: 0.421 AC: 4443 AN: 10558

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

European-Non Finnish (NFE) AF: 0.323 AC: 21936 AN: 67940

Other (OTH) AF: 0.410 AC: 865 AN: 2110

Alfa AF: 0.372 Hom.: 4581

Bravo AF: 0.459

Asia WGS AF: 0.359 AC: 1248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.36
PhyloP100		-0.93
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: rs632951; hg19: chr11-134034305;