Genetic Variant ZNF416:p.Pro189Pro (chr19-57573337-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_017879.3(ZNF416):c.567G>A(p.Pro189Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000894 in 1,614,246 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00093 ( 1 hom. )

Consequence

ZNF416
NM_017879.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.17

Variant links:

Genes affected

ZNF416 (HGNC:20645): (zinc finger protein 416) 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 cardiac muscle hypertrophy; negative regulation of cell growth involved in cardiac muscle cell development; and negative regulation of protein phosphorylation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF416 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 19-57573337-C-T is Benign according to our data. Variant chr19-57573337-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650574.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.17 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF416	NM_017879.3 link	c.567G>A	p.Pro189Pro	synonymous_variant	Exon 4 of 4	ENST00000196489.4	NP_060349.1	Q9BWM5
ZNF416	NM_001353405.2 link	c.351G>A	p.Pro117Pro	synonymous_variant	Exon 3 of 3		NP_001340334.1
ZNF416	XM_024451594.2 link	c.507G>A	p.Pro169Pro	synonymous_variant	Exon 5 of 5		XP_024307362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF416	ENST00000196489.4 link	c.567G>A	p.Pro189Pro	synonymous_variant	Exon 4 of 4	1	NM_017879.3	ENSP00000196489.2		Q9BWM5

Frequencies

GnomAD3 genomes

AF:

0.000512

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000593

AC:

149

AN:

251332

Hom.:

AF XY:

0.000648

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.000941

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000934

AC:

1365

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000901

AC XY:

655

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000893

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.000512

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000621

Hom.:

Bravo

AF:

0.000419

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZNF416: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.6

DANN

Benign

0.58

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