Variant 19-57908986-G-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_152475.3(ZNF417):c.1292C>T(p.Thr431Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,613,960 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 2 hom. )

Consequence

ZNF417
NM_152475.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.936

Variant links:

Genes affected

ZNF417 (HGNC:20646): (zinc finger protein 417) 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 be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF417 links:

ENSG00000269476 (HGNC:):

ENSG00000269476 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=0.05784732).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF417	NM_152475.3 link	c.1292C>T	p.Thr431Ile	missense_variant	3/3	ENST00000312026.6	NP_689688.2	Q8TAU3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF417	ENST00000312026.6 link	c.1292C>T	p.Thr431Ile	missense_variant	3/3	1	NM_152475.3	ENSP00000311319.4	Q8TAU3-1
ZNF417	ENST00000595559.1 link	c.1289C>T	p.Thr430Ile	missense_variant	3/3	1		ENSP00000472272.1	M0R230
ENSG00000269476	ENST00000602124.1 link	n.34+3074C>T		intron_variant		3		ENSP00000470782.1	M0QZU9
ZNF417	ENST00000594396.1 link	c.106+3074C>T		intron_variant		3		ENSP00000472352.1	M0R267

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00230

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000438

AC:

110

AN:

251242

Hom.:

AF XY:

0.000390

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000625

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.000788

AC:

1152

AN:

1461810

Hom.:

Cov.:

AF XY:

0.000733

AC XY:

533

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.000932

Gnomad4 OTH exome

AF:

0.000944

GnomAD4 genome

AF:

0.000664

AC:

101

AN:

152150

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000821

Hom.:

Bravo

AF:

0.000616

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000379

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.000771

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

Jul 15, 2021

The c.1292C>T (p.T431I) alteration is located in exon 3 (coding exon 3) of the ZNF417 gene. This alteration results from a C to T substitution at nucleotide position 1292, causing the threonine (T) at amino acid position 431 to be replaced by an isoleucine (I). 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

Pathogenic

0.65

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.43

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-5.8

D;.

REVEL

Benign

0.036

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.022

D;D

Polyphen

0.99

D;.

Vest4

0.21

MVP

0.62

ClinPred

0.16

GERP RS

1.0

Varity_R

0.12

gMVP

0.021

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