chr11-134153196-T-G

Position:

• chr11-134153196-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015261.3(NCAPD3):​c.4332A>C​(p.Lys1444Asn) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NCAPD3 NM_015261.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073862106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAPD3	NM_015261.3	c.4332A>C	p.Lys1444Asn	missense_variant	34/35	ENST00000534548.7	NP_056076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCAPD3	ENST00000534548.7	c.4332A>C	p.Lys1444Asn	missense_variant	34/35	1	NM_015261.3	ENSP00000433681.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2022

The c.4332A>C (p.K1444N) alteration is located in exon 34 (coding exon 34) of the NCAPD3 gene. This alteration results from a A to C substitution at nucleotide position 4332, causing the lysine (K) at amino acid position 1444 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.038
Sift	Benign	0.15	T
Sift4G	Benign	0.47	T
Polyphen		0.067	B
Vest4		0.34
MutPred		0.14		Loss of ubiquitination at K1444 (P = 0.0017);
MVP		0.29
MPC		0.092
ClinPred		0.20	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.087
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-134023091;