Genetic Variant ZNF14:p.Thr427Asn (chr19-19712001-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021030.3(ZNF14):c.1280C>A(p.Thr427Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,800 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: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF14
NM_021030.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.624

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:

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ACMG classification

Classification made for transcript

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=0.1517174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF14	NM_021030.3 link	c.1280C>A	p.Thr427Asn	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.1280C>A	p.Thr427Asn	missense_variant	Exon 4 of 4	1	NM_021030.3	ENSP00000340514.2		P17017

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251200

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1280C>A (p.T427N) 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 1280, causing the threonine (T) at amino acid position 427 to be replaced by an asparagine (N). 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

0.13

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.050

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.00042

LIST_S2

Benign

0.15

M_CAP

Benign

0.0016

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.1

REVEL

Benign

0.024

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.95

Vest4

0.080

MutPred

0.34

Gain of ubiquitination at K426 (P = 0.0632);

MVP

0.38

MPC

0.27

ClinPred

0.45

GERP RS

0.68

Varity_R

0.18

gMVP

0.015

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