Variant 16-87411983-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015144.3(ZCCHC14):c.2738C>T(p.Pro913Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,607,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ZCCHC14
NM_015144.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.448

Variant links:

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]

ZCCHC14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11339024).

BS2

High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC14	NM_015144.3 link	c.2738C>T	p.Pro913Leu	missense_variant	12/13	ENST00000671377.2	NP_055959.2	Q8WYQ9
ZCCHC14	XM_005255858.4 link	c.2738C>T	p.Pro913Leu	missense_variant	12/12		XP_005255915.3	Q8WYQ9
ZCCHC14	XM_017023082.3 link	c.2219C>T	p.Pro740Leu	missense_variant	12/12		XP_016878571.1
ZCCHC14	XR_243401.4 link	n.3524C>T		non_coding_transcript_exon_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZCCHC14	ENST00000671377.2 link	c.2738C>T	p.Pro913Leu	missense_variant	12/13		NM_015144.3	ENSP00000499622.1	A0A590UJW6
ZCCHC14	ENST00000268616.9 link	c.2327C>T	p.Pro776Leu	missense_variant	12/13	1		ENSP00000268616.4	Q8WYQ9-1
ZCCHC14	ENST00000568020.6 link	n.2357C>T		non_coding_transcript_exon_variant	12/14	1		ENSP00000455431.2	A0A5F9XIK1
ZCCHC14	ENST00000561928.1 link	c.1976C>T	p.Pro659Leu	missense_variant	10/10	5		ENSP00000456499.1	H3BS18

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000861

AC:

AN:

232366

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

128316

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1455630

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

723850

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000225

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:

0.0000207

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000586

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000838

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.2327C>T (p.P776L) alteration is located in exon 12 (coding exon 12) of the ZCCHC14 gene. This alteration results from a C to T substitution at nucleotide position 2327, causing the proline (P) at amino acid position 776 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

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.84

M_CAP

Benign

0.020

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

REVEL

Benign

0.055

Sift

Benign

0.044

Sift4G

Uncertain

0.014

Polyphen

0.58

Vest4

0.23

MutPred

0.25

Loss of glycosylation at P776 (P = 0.0056);

MVP

0.043

MPC

0.25

ClinPred

0.12

GERP RS

2.3

Varity_R

0.029

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over