Variant 16-87411887-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015144.3(ZCCHC14):c.2834A>G(p.Asn945Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000726 in 1,598,298 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

ZCCHC14
NM_015144.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.921

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013362527).

BS2

High AC in GnomAd at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZCCHC14	NM_015144.3 linkuse as main transcript	c.2834A>G	p.Asn945Ser	missense_variant	12/13	ENST00000671377.2
ZCCHC14	XM_005255858.4 linkuse as main transcript	c.2834A>G	p.Asn945Ser	missense_variant	12/12
ZCCHC14	XM_017023082.3 linkuse as main transcript	c.2315A>G	p.Asn772Ser	missense_variant	12/12
ZCCHC14	XR_243401.4 linkuse as main transcript	n.3620A>G		non_coding_transcript_exon_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZCCHC14	ENST00000671377.2 linkuse as main transcript	c.2834A>G	p.Asn945Ser	missense_variant	12/13		NM_015144.3	P1
ZCCHC14	ENST00000268616.9 linkuse as main transcript	c.2423A>G	p.Asn808Ser	missense_variant	12/13	1			Q8WYQ9-1
ZCCHC14	ENST00000568020.6 linkuse as main transcript	c.2456A>G	p.Asn819Ser	missense_variant, NMD_transcript_variant	12/14	1
ZCCHC14	ENST00000561928.1 linkuse as main transcript	c.2075A>G	p.Asn692Ser	missense_variant	10/10	5

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000193

AC:

AN:

217842

Hom.:

AF XY:

0.000219

AC XY:

AN XY:

118604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000131

Gnomad ASJ exome

AF:

0.00309

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000354

Gnomad FIN exome

AF:

0.0000549

Gnomad NFE exome

AF:

0.0000516

Gnomad OTH exome

AF:

0.000370

GnomAD4 exome

AF:

0.0000726

AC:

105

AN:

1446176

Hom.:

Cov.:

AF XY:

0.0000822

AC XY:

AN XY:

718190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000119

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.0000196

Gnomad4 NFE exome

AF:

0.0000208

Gnomad4 OTH exome

AF:

0.000134

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000266

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.000116

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

Nov 27, 2023

The c.2423A>G (p.N808S) alteration is located in exon 12 (coding exon 12) of the ZCCHC14 gene. This alteration results from a A to G substitution at nucleotide position 2423, causing the asparagine (N) at amino acid position 808 to be replaced by a serine (S). 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

0.055

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.72

Cadd

Benign

Dann

Benign

0.62

DEOGEN2

Benign

0.030

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.74

M_CAP

Benign

0.0060

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.74

MutationTaster

Benign

0.86

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.52

REVEL

Benign

0.024

Sift

Benign

0.21

Sift4G

Benign

0.95

Polyphen

0.0070

Vest4

0.20

MVP

0.043

MPC

0.20

ClinPred

0.021

GERP RS

-0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.036

gMVP

0.13

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