Variant 19-36340714-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020917.3(ZFP14):c.1112A>T(p.Lys371Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00638 in 1,614,100 control chromosomes in the GnomAD database, including 48 homozygotes. 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 0.0037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 48 hom. )

Consequence

ZFP14
NM_020917.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.90

Variant links:

Genes affected

ZFP14 (HGNC:29312): (ZFP14 zinc finger protein) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within blastocyst hatching. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFP14 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=0.0058351755).

BS2

High Homozygotes in GnomAdExome4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP14	NM_020917.3 link	c.1112A>T	p.Lys371Met	missense_variant	5/5	ENST00000270001.12	NP_065968.1	Q9HCL3
ZFP14	NM_001297619.2 link	c.1115A>T	p.Lys372Met	missense_variant	5/5		NP_001284548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP14	ENST00000270001.12 link	c.1112A>T	p.Lys371Met	missense_variant	5/5	1	NM_020917.3	ENSP00000270001.6		Q9HCL3

Frequencies

GnomAD3 genomes

AF:

0.00369

AC:

561

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00620

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00339

AC:

851

AN:

251284

Hom.:

AF XY:

0.00330

AC XY:

448

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00408

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.000972

Gnomad NFE exome

AF:

0.00604

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00666

AC:

9736

AN:

1461776

Hom.:

Cov.:

AF XY:

0.00642

AC XY:

4671

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00150

Gnomad4 ASJ exome

AF:

0.00440

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000545

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00815

Gnomad4 OTH exome

AF:

0.00583

GnomAD4 genome

AF:

0.00368

AC:

561

AN:

152324

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

247

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00620

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00654

Hom.:

Bravo

AF:

0.00397

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00322

AC:

391

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00556

EpiControl

AF:

0.00670

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

Feb 10, 2023

The c.1112A>T (p.K371M) alteration is located in exon 5 (coding exon 4) of the ZFP14 gene. This alteration results from a A to T substitution at nucleotide position 1112, causing the lysine (K) at amino acid position 371 to be replaced by a methionine (M). 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

0.20

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

Eigen

Benign

0.11

Eigen_PC

Benign

0.025

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.22

M_CAP

Benign

0.0095

MetaRNN

Benign

0.0058

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.98

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.20

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0060

Polyphen

0.90

Vest4

0.28

MVP

0.055

MPC

1.4

ClinPred

0.041

GERP RS

2.8

Varity_R

0.43

gMVP

0.11

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