Variant chr19-57702000-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001085384.3(ZNF154):c.949A>T(p.Ile317Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,556 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF154
NM_001085384.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0270

Variant links:

Genes affected

ZNF154 (HGNC:12939): (zinc finger protein 154) This gene encodes a protein that belongs to the zinc finger Kruppel family of transcriptional regulators, whose members are thought to function in normal and abnormal cell growth and differentiation. Hypermethylation of this gene is associated with the recurrence of non muscle invasive bladder cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ZNF154 links:

ZNF551 (HGNC:25108): (zinc finger protein 551) 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]

ZNF551 links:

Genome browser will be placed here

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=0.1290093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF154	NM_001085384.3 linkuse as main transcript	c.949A>T	p.Ile317Phe	missense_variant	3/3	ENST00000684351.1	NP_001078853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF154	ENST00000684351.1 linkuse as main transcript	c.949A>T	p.Ile317Phe	missense_variant	3/3		NM_001085384.3	ENSP00000507206	P1
ZNF154	ENST00000512439.6 linkuse as main transcript	c.949A>T	p.Ile317Phe	missense_variant	3/4	1		ENSP00000421258	P1
ZNF551	ENST00000596085.1 linkuse as main transcript	c.158-15167T>A		intron_variant		2		ENSP00000472230
ZNF154	ENST00000451275.1 linkuse as main transcript	c.949A>T	p.Ile317Phe	missense_variant, NMD_transcript_variant	3/5	2		ENSP00000469633

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250926

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135846

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461556

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727090

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2024

The c.949A>T (p.I317F) alteration is located in exon 3 (coding exon 3) of the ZNF154 gene. This alteration results from a A to T substitution at nucleotide position 949, causing the isoleucine (I) at amino acid position 317 to be replaced by a phenylalanine (F). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.21

M_CAP

Benign

0.0024

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.43

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.032

Sift

Uncertain

0.0010

Sift4G

Benign

0.099

Polyphen

0.88

Vest4

0.13

MutPred

0.28

Loss of stability (P = 0.1135);

MVP

0.21

MPC

0.61

ClinPred

0.70

GERP RS

1.8

Varity_R

0.32

gMVP

0.054

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