Variant chr19-52929180-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001202473.2(ZNF816-ZNF321P):c.425A>G(p.His142Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,614,094 control chromosomes in the GnomAD database, including 7 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H142Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 7 hom. )

Consequence

ZNF816-ZNF321P
NM_001202473.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.474

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013365835).

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF816-ZNF321P	NM_001202473.2 linkuse as main transcript	c.425A>G	p.His142Arg	missense_variant	4/4
ZNF321P	NR_037805.1 linkuse as main transcript	n.289A>G		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.296A>G		non_coding_transcript_exon_variant	2/2	2
ZNF321P	ENST00000550843.1 linkuse as main transcript	n.218A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.000946

AC:

144

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00188

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000958

AC:

241

AN:

251460

Hom.:

AF XY:

0.000876

AC XY:

119

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00191

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.00148

AC:

2165

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

1012

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00187

Gnomad4 OTH exome

AF:

0.000811

GnomAD4 genome

AF:

0.000946

AC:

144

AN:

152234

Hom.:

Cov.:

AF XY:

0.000807

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00188

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000503

Hom.:

Bravo

AF:

0.000910

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000923

AC:

112

EpiCase

AF:

0.00185

EpiControl

AF:

0.00225

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 26, 2022

The c.425A>G (p.H142R) alteration is located in exon 4 (coding exon 3) of the ZNF816-ZNF321P gene. This alteration results from a A to G substitution at nucleotide position 425, causing the histidine (H) at amino acid position 142 to be replaced by an arginine (R). 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

-0.65

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.2

DANN

Benign

0.38

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.30

M_CAP

Benign

0.0021

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.015

Sift

Benign

0.22

Sift4G

Benign

0.28

Vest4

0.16

MVP

0.040

MPC

0.021

ClinPred

0.016

GERP RS

-1.4

gMVP

0.065

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