Genetic Variant NCAPG:p.Leu999Val (chr4-17843372-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022346.5(NCAPG):c.2995C>G(p.Leu999Val) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L999I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NCAPG
NM_022346.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.510

Publications

0 publications found

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]

NCAPG links:

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]

LCORL links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07287267).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022346.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCAPG	NM_022346.5	MANE Select	c.2995C>G	p.Leu999Val	missense	Exon 21 of 21	NP_071741.2
LCORL	NM_001394446.1	MANE Select	c.*2516G>C		3_prime_UTR	Exon 8 of 8	NP_001381375.1	A0A1B0GVP4
LCORL	NM_001365660.1		c.*2349G>C		3_prime_UTR	Exon 8 of 8	NP_001352589.1	A0A6Q8PHE0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCAPG	ENST00000251496.7	TSL:1 MANE Select	c.2995C>G	p.Leu999Val	missense	Exon 21 of 21	ENSP00000251496.2	Q9BPX3
LCORL	ENST00000635767.2	TSL:5 MANE Select	c.*2516G>C		3_prime_UTR	Exon 8 of 8	ENSP00000490600.1	A0A1B0GVP4
LCORL	ENST00000326877.8	TSL:1	c.*2349G>C		3_prime_UTR	Exon 7 of 7	ENSP00000317566.3	Q8N3X6-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0070

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.020

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

PhyloP100

0.51

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.96

REVEL

Benign

0.10

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.019

Polyphen

0.57

Vest4

0.22

MutPred

0.27

Gain of glycosylation at T996 (P = 0.0043)

MVP

0.40

MPC

0.34

ClinPred

0.48

GERP RS

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.055

gMVP

0.35

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over