Genetic Variant ZNF14:p.Ala595Asp (chr19-19711497-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021030.3(ZNF14):c.1784C>A(p.Ala595Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZNF14
NM_021030.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.11

Variant links:

Genes affected

ZNF14 (HGNC:12924): (zinc finger protein 14) The protein encoded by this gene contains a zinc finger and a Kruppel-associated box (KRAB) domain. KRAB domain is known to be involved in the transcriptional repression of a number of zinc finger proteins. [provided by RefSeq, Jul 2008]

ZNF14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29578155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF14	NM_021030.3 link	c.1784C>A	p.Ala595Asp	missense_variant	Exon 4 of 4	ENST00000344099.4	NP_066358.2	P17017

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF14	ENST00000344099.4 link	c.1784C>A	p.Ala595Asp	missense_variant	Exon 4 of 4	1	NM_021030.3	ENSP00000340514.2		P17017

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152018

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727134

show subpopulations

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:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152018

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74270

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1784C>A (p.A595D) alteration is located in exon 4 (coding exon 4) of the ZNF14 gene. This alteration results from a C to A substitution at nucleotide position 1784, causing the alanine (A) at amino acid position 595 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

Benign

0.32

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.00014

LIST_S2

Benign

0.44

M_CAP

Benign

0.0028

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.093

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.18

MutPred

0.53

Loss of MoRF binding (P = 0.0717);

MVP

0.50

MPC

0.47

ClinPred

0.98

GERP RS

0.69

Varity_R

0.69

gMVP

0.013

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