Variant chr19-52929262-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001202473.2(ZNF816-ZNF321P):c.343T>A(p.Phe115Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

ZNF816-ZNF321P
NM_001202473.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10

Variant links:

Genes affected

ZNF816-ZNF321P (HGNC:):

ZNF816-ZNF321P links:

ZNF321P (HGNC:13827): (zinc finger protein 321, pseudogene)

ZNF321P 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=0.022429883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF816-ZNF321P	NM_001202473.2 linkuse as main transcript	c.343T>A	p.Phe115Ile	missense_variant	4/4
ZNF321P	NR_037805.1 linkuse as main transcript	n.207T>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF321P	ENST00000313956.4 linkuse as main transcript	n.214T>A		non_coding_transcript_exon_variant	2/2	2
ZNF321P	ENST00000550843.1 linkuse as main transcript	n.136T>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000295

AC:

AN:

251184

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000326

AC:

476

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

234

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.000367

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000322

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000340

Hom.:

Bravo

AF:

0.000268

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000296

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

Jan 19, 2024

The c.343T>A (p.F115I) alteration is located in exon 4 (coding exon 3) of the ZNF816-ZNF321P gene. This alteration results from a T to A substitution at nucleotide position 343, causing the phenylalanine (F) at amino acid position 115 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

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.94

DANN

Benign

0.96

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.54

M_CAP

Benign

0.0038

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.029

Sift

Benign

0.15

Sift4G

Benign

0.15

Vest4

0.13

MVP

0.048

MPC

0.046

ClinPred

0.073

GERP RS

-0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.073

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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