chr16-87411620-C-T

Position:

• chr16-87411620-C-T

Variant summary

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

The NM_015144.3(ZCCHC14):​c.3101G>A​(p.Gly1034Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 33)
• Consequence: ZCCHC14 NM_015144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.73

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZCCHC14	NM_015144.3	c.3101G>A	p.Gly1034Asp	missense_variant	12/13	ENST00000671377.2
ZCCHC14	XM_005255858.4	c.3101G>A	p.Gly1034Asp	missense_variant	12/12
ZCCHC14	XM_017023082.3	c.2582G>A	p.Gly861Asp	missense_variant	12/12
ZCCHC14	XR_243401.4	n.3887G>A		non_coding_transcript_exon_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZCCHC14	ENST00000671377.2	c.3101G>A	p.Gly1034Asp	missense_variant	12/13		NM_015144.3	P1
ZCCHC14	ENST00000268616.9	c.2690G>A	p.Gly897Asp	missense_variant	12/13	1
ZCCHC14	ENST00000568020.6	c.2723G>A	p.Gly908Asp	missense_variant, NMD_transcript_variant	12/14	1
ZCCHC14	ENST00000561928.1	c.2342G>A	p.Gly781Asp	missense_variant	10/10	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Jun 17, 2024

The c.2690G>A (p.G897D) alteration is located in exon 12 (coding exon 12) of the ZCCHC14 gene. This alteration results from a G to A substitution at nucleotide position 2690, causing the glycine (G) at amino acid position 897 to be replaced by an aspartic acid (D). 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	0.64
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.10	D
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.34		Gain of solvent accessibility (P = 0.0281);
MVP		0.96
MPC		0.32
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.48
gMVP		0.51

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

LitVar

Other links and lift over

dbSNP: rs1849093106; hg19: chr16-87445226;