chr11-134153015-C-A

Variant names:

• chr11-134153015-C-A
• rs768995468
• NM_015261.3:c.4426G>T

Variant summary

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

The NM_015261.3(NCAPD3):​c.4426G>T​(p.Ala1476Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCAPD3 NM_015261.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.864

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD3	NM_015261.3	c.4426G>T	p.Ala1476Ser	missense_variant	Exon 35 of 35	ENST00000534548.7	NP_056076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAPD3	ENST00000534548.7	c.4426G>T	p.Ala1476Ser	missense_variant	Exon 35 of 35	1	NM_015261.3	ENSP00000433681.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1440228 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 713312

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.023
Sift	Benign	0.14	T
Sift4G	Benign	0.30	T
Polyphen		0.61	P
Vest4		0.087
MutPred		0.16		Gain of relative solvent accessibility (P = 0.0023);
MVP		0.26
MPC		0.13
ClinPred		0.36	T
GERP RS		3.7
Varity_R		0.030
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: -5

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

Publications

LitVar

Other links and lift over

dbSNP: rs768995468; hg19: chr11-134022910; COSMIC: COSV100137873; COSMIC: COSV100137873;