4-17812342-C-T

Position:

• chr4-17812342-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022346.5(NCAPG):​c.233C>T​(p.Ser78Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCAPG NM_022346.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.20

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAPG	NM_022346.5	c.233C>T	p.Ser78Leu	missense_variant	2/21	ENST00000251496.7	NP_071741.2
NCAPG	XM_017008543.3	c.233C>T	p.Ser78Leu	missense_variant	2/21		XP_016864032.1
NCAPG	NR_073124.2	n.332C>T		non_coding_transcript_exon_variant	2/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCAPG	ENST00000251496.7	c.233C>T	p.Ser78Leu	missense_variant	2/21	1	NM_022346.5	ENSP00000251496.2
NCAPG	ENST00000514176.5	n.233C>T		non_coding_transcript_exon_variant	2/20	1		ENSP00000423042.1
NCAPG	ENST00000513226.1	n.283C>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 03, 2024

The c.233C>T (p.S78L) alteration is located in exon 2 (coding exon 2) of the NCAPG gene. This alteration results from a C to T substitution at nucleotide position 233, causing the serine (S) at amino acid position 78 to be replaced by a leucine (L). 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	0.11
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.65		Loss of disorder (P = 0.0172);
MVP		0.40
MPC		0.22
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.44
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-17813965;