Variant 16-87411855-C-T 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.2866G>A(p.Val956Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000051 in 1,607,490 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: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

ZCCHC14
NM_015144.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0200

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=0.022688776).

BS2

High AC in GnomAdExome4 at 79 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC14	NM_015144.3 link	c.2866G>A	p.Val956Met	missense_variant	12/13	ENST00000671377.2	NP_055959.2	Q8WYQ9
ZCCHC14	XM_005255858.4 link	c.2866G>A	p.Val956Met	missense_variant	12/12		XP_005255915.3	Q8WYQ9
ZCCHC14	XM_017023082.3 link	c.2347G>A	p.Val783Met	missense_variant	12/12		XP_016878571.1
ZCCHC14	XR_243401.4 link	n.3652G>A		non_coding_transcript_exon_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZCCHC14	ENST00000671377.2 link	c.2866G>A	p.Val956Met	missense_variant	12/13		NM_015144.3	ENSP00000499622.1	A0A590UJW6
ZCCHC14	ENST00000268616.9 link	c.2455G>A	p.Val819Met	missense_variant	12/13	1		ENSP00000268616.4	Q8WYQ9-1
ZCCHC14	ENST00000568020.6 link	n.2485G>A		non_coding_transcript_exon_variant	12/14	1		ENSP00000455431.2	A0A5F9XIK1
ZCCHC14	ENST00000561928.1 link	c.2104G>A	p.Val702Met	missense_variant	10/10	5		ENSP00000456499.1	H3BS18

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000212

AC:

AN:

235864

Hom.:

AF XY:

0.0000390

AC XY:

AN XY:

128064

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:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000377

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000543

AC:

AN:

1455324

Hom.:

Cov.:

AF XY:

0.0000428

AC XY:

AN XY:

723616

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000640

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000283

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.028

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.031

M_CAP

Benign

0.011

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.075

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.81

REVEL

Benign

0.021

Sift

Benign

0.60

Sift4G

Benign

0.15

Polyphen

0.0070

Vest4

0.096

MVP

0.068

MPC

0.25

ClinPred

0.012

GERP RS

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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