Genetic Variant ZNF479:p.Ile346Thr (chr7-57120378-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001370129.2(ZNF479):c.1037T>C(p.Ile346Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,611,692 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 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ZNF479
NM_001370129.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.346

Variant links:

Genes affected

ZNF479 (HGNC:23258): (zinc finger protein 479) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF479 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024581075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF479	NM_001370129.2 link	c.1037T>C	p.Ile346Thr	missense_variant	Exon 4 of 4	ENST00000319636.10	NP_001357058.1
ZNF479	NM_033273.3 link	c.1037T>C	p.Ile346Thr	missense_variant	Exon 5 of 5		NP_150376.1	Q96JC4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF479	ENST00000319636.10 link	c.1037T>C	p.Ile346Thr	missense_variant	Exon 4 of 4	1	NM_001370129.2	ENSP00000324518.6		Q96JC4
ZNF479	ENST00000331162.8 link	c.1037T>C	p.Ile346Thr	missense_variant	Exon 5 of 5	1		ENSP00000333776.4		Q96JC4

Frequencies

GnomAD3 genomes

AF:

0.000140

AC:

AN:

150472

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000331

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000632

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000182

AC:

AN:

247436

Hom.:

AF XY:

0.000201

AC XY:

AN XY:

134322

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000295

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000196

Gnomad OTH exome

AF:

0.000500

GnomAD4 exome

AF:

0.000106

AC:

155

AN:

1461102

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

726824

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000426

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000657

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000139

AC:

AN:

150590

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

73554

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.000331

Gnomad4 ASJ

AF:

0.000578

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000632

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000389

Hom.:

ExAC

AF:

0.000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1037T>C (p.I346T) alteration is located in exon 5 (coding exon 4) of the ZNF479 gene. This alteration results from a T to C substitution at nucleotide position 1037, causing the isoleucine (I) at amino acid position 346 to be replaced by a threonine (T). 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

0.68

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.055

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.072

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.0012

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.57

N;N

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-4.4

D;.

REVEL

Benign

0.034

Sift

Benign

0.061

T;.

Sift4G

Benign

0.061

T;T

Polyphen

0.11

B;B

Vest4

0.13

MVP

0.13

MPC

1.1

ClinPred

0.0092

GERP RS

0.95

Varity_R

0.046

gMVP

0.0058

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