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GeneBe

4-17842337-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022346.5(NCAPG):c.2882G>A(p.Arg961Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

NCAPG
NM_022346.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.966
Variant links:
Genes affected
NCAPG (HGNC:24304): (non-SMC condensin I complex subunit G) This gene encodes a subunit of the condensin complex, which is responsible for the condensation and stabilization of chromosomes during mitosis and meiosis. Phosphorylation of the encoded protein activates the condensin complex. There are pseudogenes for this gene on chromosomes 8 and 15. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
LCORL (HGNC:30776): (ligand dependent nuclear receptor corepressor like) This gene encodes a transcription factor that appears to function in spermatogenesis. Polymorphisms in this gene are associated with measures of skeletal frame size and adult height. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.030852348).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NCAPGNM_022346.5 linkuse as main transcriptc.2882G>A p.Arg961Lys missense_variant 20/21 ENST00000251496.7
LCORLNM_001394446.1 linkuse as main transcriptc.*3551C>T 3_prime_UTR_variant 8/8 ENST00000635767.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NCAPGENST00000251496.7 linkuse as main transcriptc.2882G>A p.Arg961Lys missense_variant 20/211 NM_022346.5 P1
LCORLENST00000635767.2 linkuse as main transcriptc.*3551C>T 3_prime_UTR_variant 8/85 NM_001394446.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000558
AC:
14
AN:
250898
Hom.:
0
AF XY:
0.0000590
AC XY:
8
AN XY:
135622
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000406
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:
0.00
GnomAD4 exome
AF:
0.00000890
AC:
13
AN:
1460116
Hom.:
0
Cov.:
30
AF XY:
0.00000826
AC XY:
6
AN XY:
726374
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000291
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.:
32
Bravo
AF:
0.0000227
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 08, 2024The c.2882G>A (p.R961K) alteration is located in exon 20 (coding exon 20) of the NCAPG gene. This alteration results from a G to A substitution at nucleotide position 2882, causing the arginine (R) at amino acid position 961 to be replaced by a lysine (K). 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
0.066
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.71
Cadd
Benign
15
Dann
Benign
0.85
DEOGEN2
Benign
0.0023
T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.65
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.031
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.94
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
0.21
N
REVEL
Benign
0.052
Sift
Benign
0.58
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.22
MutPred
0.26
Gain of glycosylation at T962 (P = 0.0052);
MVP
0.20
MPC
0.15
ClinPred
0.020
T
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.029
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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.

Other links and lift over

dbSNP: rs748965808; hg19: chr4-17843960; API