4-17811151-C-T

Variant summary

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

The NM_022346.5(NCAPG):c.74C>T(p.Ala25Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000102 in 1,366,290 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: NCAPG NM_022346.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03

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]

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/exons	MANE	UniProt
NCAPG	NM_022346.5	c.74C>T	p.Ala25Val	missense_variant	1/21	ENST00000251496.7
NCAPG	XM_017008543.3	c.74C>T	p.Ala25Val	missense_variant	1/21
NCAPG	NR_073124.2	n.173C>T		non_coding_transcript_exon_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAPG	ENST00000251496.7	c.74C>T	p.Ala25Val	missense_variant	1/21	1	NM_022346.5	P1
NCAPG	ENST00000514176.5	c.74C>T	p.Ala25Val	missense_variant, NMD_transcript_variant	1/20	1
NCAPG	ENST00000513226.1	n.124C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000102 AC: 14 AN: 1366290 Hom.: 0 Cov.: 31 AF XY: 0.0000133 AC XY: 9 AN XY: 674222

Gnomad4 AFR exome AF: 0.000211

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: 0.00000657

Gnomad4 OTH exome AF: 0.0000178

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.74C>T (p.A25V) alteration is located in exon 1 (coding exon 1) of the NCAPG gene. This alteration results from a C to T substitution at nucleotide position 74, causing the alanine (A) at amino acid position 25 to be replaced by a valine (V). 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	0.23
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
Cadd	Pathogenic	30
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.18
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.43		Gain of methylation at K26 (P = 0.0583);
MVP		0.44
MPC		0.52
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Varity_R		0.67
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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

Other links and lift over

dbSNP: rs1410270071; hg19: chr4-17812774;