chr2-96342786-C-T

Position:

• chr2-96342786-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015341.5(NCAPH):​c.394C>T​(p.His132Tyr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCAPH NM_015341.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

Genes affected

NCAPH (HGNC:1112): (non-SMC condensin I complex subunit H) This gene encodes a member of the barr gene family and a regulatory subunit of the condensin complex. This complex is required for the conversion of interphase chromatin into condensed chromosomes. The protein encoded by this gene is associated with mitotic chromosomes, except during the early phase of chromosome condensation. During interphase, the protein has a distinct punctate nucleolar localization. Alternatively spliced transcript variants encoding different proteins have been described. [provided by RefSeq, Jul 2013]

NCAPH (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.892

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAPH	NM_015341.5	c.394C>T	p.His132Tyr	missense_variant	4/18	ENST00000240423.9	NP_056156.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCAPH	ENST00000240423.9	c.394C>T	p.His132Tyr	missense_variant	4/18	1	NM_015341.5	ENSP00000240423.4

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

Nov 13, 2024

The c.394C>T (p.H132Y) alteration is located in exon 4 (coding exon 4) of the NCAPH gene. This alteration results from a C to T substitution at nucleotide position 394, causing the histidine (H) at amino acid position 132 to be replaced by a tyrosine (Y). 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	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.89	D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	3.3	M;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.72
MutPred		0.77		Gain of helix (P = 0.1736);.;.;
MVP		0.69
MPC		0.78
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.54
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-97008524;