16-87411696-C-G

Position:

• chr16-87411696-C-G

Variant summary

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

The NM_015144.3(ZCCHC14):​c.3025G>C​(p.Val1009Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZCCHC14 NM_015144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60

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=0.25911254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC14	NM_015144.3	c.3025G>C	p.Val1009Leu	missense_variant	12/13	ENST00000671377.2	NP_055959.2
ZCCHC14	XM_005255858.4	c.3025G>C	p.Val1009Leu	missense_variant	12/12		XP_005255915.3
ZCCHC14	XM_017023082.3	c.2506G>C	p.Val836Leu	missense_variant	12/12		XP_016878571.1
ZCCHC14	XR_243401.4	n.3811G>C		non_coding_transcript_exon_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCCHC14	ENST00000671377.2	c.3025G>C	p.Val1009Leu	missense_variant	12/13		NM_015144.3	ENSP00000499622.1
ZCCHC14	ENST00000268616.9	c.2614G>C	p.Val872Leu	missense_variant	12/13	1		ENSP00000268616.4
ZCCHC14	ENST00000568020.6	n.2644G>C		non_coding_transcript_exon_variant	12/14	1		ENSP00000455431.2
ZCCHC14	ENST00000561928.1	c.2263G>C	p.Val755Leu	missense_variant	10/10	5		ENSP00000456499.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461730 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

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

Dec 06, 2024

The c.2614G>C (p.V872L) alteration is located in exon 12 (coding exon 12) of the ZCCHC14 gene. This alteration results from a G to C substitution at nucleotide position 2614, causing the valine (V) at amino acid position 872 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	0.22
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.053
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.17
Sift	Benign	0.20	T
Sift4G	Benign	0.16	T
Polyphen		0.69	P
Vest4		0.51
MutPred		0.082		Gain of helix (P = 0.1736);
MVP		0.11
MPC		0.25
ClinPred		0.24	T
GERP RS		4.6
Varity_R		0.080
gMVP		0.19

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: chr16-87445302;