chr10-79394284-G-T

Position:

• chr10-79394284-G-T

Variant summary

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

The NM_153367.4(ZCCHC24):​c.604C>A​(p.His202Asn) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 33)
• Consequence: ZCCHC24 NM_153367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.35

Genes affected

ZCCHC24 (HGNC:26911): (zinc finger CCHC-type containing 24) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000235426 (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, 0.846

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC24	NM_153367.4	c.604C>A	p.His202Asn	missense_variant	3/4	ENST00000372336.4	NP_699198.2
ZCCHC24	XM_011539452.4	c.394C>A	p.His132Asn	missense_variant	3/4		XP_011537754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCCHC24	ENST00000372336.4	c.604C>A	p.His202Asn	missense_variant	3/4	1	NM_153367.4	ENSP00000361411.3
ZCCHC24	ENST00000372333.3	c.425C>A	p.Thr142Lys	missense_variant	3/4	2		ENSP00000361408.3
ENSG00000235426	ENST00000438554.2	n.259+11698G>T		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Oct 04, 2024

The c.604C>A (p.H202N) alteration is located in exon 3 (coding exon 3) of the ZCCHC24 gene. This alteration results from a C to A substitution at nucleotide position 604, causing the histidine (H) at amino acid position 202 to be replaced by an asparagine (N). 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	Pathogenic	1.0
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	31
DANN	Benign	0.91
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.9	L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.82
MutPred		0.62		Loss of ubiquitination at K203 (P = 0.0982);
MVP		0.11
MPC		2.0
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.71
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-81154040;