16-87412040-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015144.3(ZCCHC14):c.2681C>A(p.Pro894His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZCCHC14 NM_015144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.12

Genes affected

ZCCHC14 (HGNC:24134): (zinc finger CCHC-type containing 14) Predicted to enable nucleic acid binding activity; phosphatidylinositol binding activity; and zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25986242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZCCHC14	NM_015144.3	c.2681C>A	p.Pro894His	missense_variant	12/13	ENST00000671377.2
ZCCHC14	XM_005255858.4	c.2681C>A	p.Pro894His	missense_variant	12/12
ZCCHC14	XM_017023082.3	c.2162C>A	p.Pro721His	missense_variant	12/12
ZCCHC14	XR_243401.4	n.3467C>A		non_coding_transcript_exon_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZCCHC14	ENST00000671377.2	c.2681C>A	p.Pro894His	missense_variant	12/13		NM_015144.3	P1
ZCCHC14	ENST00000268616.9	c.2270C>A	p.Pro757His	missense_variant	12/13	1
ZCCHC14	ENST00000568020.6	c.2303C>A	p.Pro768His	missense_variant, NMD_transcript_variant	12/14	1
ZCCHC14	ENST00000561928.1	c.1922C>A	p.Pro641His	missense_variant	10/10	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 96

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

Jan 23, 2024

The c.2270C>A (p.P757H) alteration is located in exon 12 (coding exon 12) of the ZCCHC14 gene. This alteration results from a C to A substitution at nucleotide position 2270, causing the proline (P) at amino acid position 757 to be replaced by a histidine (H). 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	0.19
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	23
Dann	Benign	0.92
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.024
Eigen_PC	Benign	-0.023
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.80	P
Vest4		0.53
MutPred		0.13		Gain of sheet (P = 0.0221);
MVP		0.043
MPC		0.29
ClinPred		0.55	D
GERP RS		4.7
Varity_R		0.18
gMVP		0.35

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: chr16-87445646;