11-134157049-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015261.3(NCAPD3):c.4221C>A(p.His1407Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,613,574 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 13 hom., cov: 32)

Exomes 𝑓: 0.013 ( 119 hom. )

Consequence

NCAPD3
NM_015261.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.26

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036039054).

BP6

Variant 11-134157049-G-T is Benign according to our data. Variant chr11-134157049-G-T is described in ClinVar as [Benign]. Clinvar id is 777871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1590/152140) while in subpopulation NFE AF= 0.0157 (1070/68000). AF 95% confidence interval is 0.015. There are 13 homozygotes in gnomad4. There are 727 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD3	NM_015261.3 link	c.4221C>A	p.His1407Gln	missense_variant	Exon 32 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.4221C>A	p.His1407Gln	missense_variant	Exon 32 of 35	1	NM_015261.3	ENSP00000433681.3		P42695

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1590

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0155

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0157

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00941

AC:

2362

AN:

251126

Hom.:

AF XY:

0.00922

AC XY:

1252

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00753

Gnomad ASJ exome

AF:

0.0168

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0128

AC:

18731

AN:

1461434

Hom.:

119

Cov.:

AF XY:

0.0126

AC XY:

9140

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.00819

Gnomad4 ASJ exome

AF:

0.0181

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000337

Gnomad4 FIN exome

AF:

0.0122

Gnomad4 NFE exome

AF:

0.0148

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

AF:

0.0105

AC:

1590

AN:

152140

Hom.:

Cov.:

AF XY:

0.00978

AC XY:

727

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.0128

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.0155

Gnomad4 NFE

AF:

0.0157

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.00917

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0132

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0121

AC:

104

ExAC

AF:

0.00925

AC:

1123

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0122

EpiControl

AF:

0.0133

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NCAPD3: BP4, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

NCAPD3-related disorder

Benign:1

Mar 06, 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

0.084

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.016

DANN

Benign

0.43

DEOGEN2

Benign

0.0042

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0036

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.21

REVEL

Benign

0.055

Sift

Benign

0.71

Sift4G

Benign

0.47

Polyphen

0.11

Vest4

0.11

MutPred

0.25

Gain of helix (P = 0.0078);

MVP

0.13

MPC

0.075

ClinPred

0.0056

GERP RS

-11

Varity_R

0.022

gMVP

0.19

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