11-134153833-A-C

Variant names:

• chr11-134153833-A-C
• rs94499
• NM_015261.3:c.4253-470T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015261.3(NCAPD3):​c.4253-470T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCAPD3 NM_015261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015261.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPD3	NM_015261.3	MANE Select	c.4253-470T>G		intron	N/A	NP_056076.1	P42695
	NCAPD3	NM_001372068.1		c.4253-470T>G		intron	N/A	NP_001358997.1	A0A8I5KT00
	NCAPD3	NM_001372065.1		c.4253-470T>G		intron	N/A	NP_001358994.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPD3	ENST00000534548.7	TSL:1 MANE Select	c.4253-470T>G		intron	N/A	ENSP00000433681.3	P42695
	NCAPD3	ENST00000525964.7	TSL:1	n.*1895-470T>G		intron	N/A	ENSP00000431612.2	E9PKK4
	NCAPD3	ENST00000685324.1		c.4253-470T>G		intron	N/A	ENSP00000508707.1	P42695

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 34664 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 17948

African (AFR) AF: 0.00 AC: 0 AN: 1094

American (AMR) AF: 0.00 AC: 0 AN: 3044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 664

East Asian (EAS) AF: 0.00 AC: 0 AN: 1790

South Asian (SAS) AF: 0.00 AC: 0 AN: 4092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 20904

Other (OTH) AF: 0.00 AC: 0 AN: 1846

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.33
DANN	Benign	0.39
PhyloP100		-0.64

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: rs94499; hg19: chr11-134023728;