Variant 11-134152972-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_015261.3(NCAPD3):c.4469G>A(p.Arg1490Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000472 in 1,570,438 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 2 hom. )

Consequence

NCAPD3
NM_015261.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.38

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007003784).

BP6

Variant 11-134152972-C-T is Benign according to our data. Variant chr11-134152972-C-T is described in ClinVar as [Benign]. Clinvar id is 3052363.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00261 (398/152274) while in subpopulation AFR AF= 0.0091 (378/41556). AF 95% confidence interval is 0.00834. There are 2 homozygotes in gnomad4. There are 186 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD3	NM_015261.3 link	c.4469G>A	p.Arg1490Gln	missense_variant	Exon 35 of 35	ENST00000534548.7	NP_056076.1	P42695

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAPD3	ENST00000534548.7 link	c.4469G>A	p.Arg1490Gln	missense_variant	Exon 35 of 35	1	NM_015261.3	ENSP00000433681.3		P42695

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

399

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00915

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000701

AC:

154

AN:

219832

Hom.:

AF XY:

0.000400

AC XY:

AN XY:

117494

show subpopulations

Gnomad AFR exome

AF:

0.00893

Gnomad AMR exome

AF:

0.000334

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000382

GnomAD4 exome

AF:

0.000243

AC:

344

AN:

1418164

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

135

AN XY:

700368

show subpopulations

Gnomad4 AFR exome

AF:

0.00901

Gnomad4 AMR exome

AF:

0.000331

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000110

Gnomad4 OTH exome

AF:

0.000462

GnomAD4 genome

AF:

0.00261

AC:

398

AN:

152274

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00910

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000622

Hom.:

Bravo

AF:

0.00282

ESP6500AA

AF:

0.00977

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000833

AC:

101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NCAPD3-related disorder

Benign:1

Dec 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0029

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.012

MetaRNN

Benign

0.0070

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.44

REVEL

Benign

0.11

Sift

Uncertain

0.013

Sift4G

Uncertain

0.043

Polyphen

1.0

Vest4

0.40

MVP

0.36

MPC

0.38

ClinPred

0.030

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.081

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over