Variant chr19-52929414-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001202473.2(ZNF816-ZNF321P):c.191A>G(p.Asp64Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00034 in 1,613,634 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 2 hom. )

Consequence

ZNF816-ZNF321P
NM_001202473.2 missense, splice_region

Scores

Splicing: ADA: 0.00004597

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.342

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.109907985).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF816-ZNF321P	NM_001202473.2 linkuse as main transcript	c.191A>G	p.Asp64Gly	missense_variant, splice_region_variant	4/4		NP_001189402.1
ZNF321P	NR_037805.1 linkuse as main transcript	n.55A>G		splice_region_variant, non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF321P	ENST00000313956.4 linkuse as main transcript	n.62A>G		splice_region_variant, non_coding_transcript_exon_variant	2/2	2
ZNF321P	ENST00000550843.1 linkuse as main transcript			upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000117

AC:

AN:

248824

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

135096

show subpopulations

Gnomad AFR exome

AF:

0.000262

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:

0.000213

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000361

AC:

527

AN:

1461292

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

248

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

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:

0.000453

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000138

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.000178

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000116

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000474

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 17, 2023

The c.191A>G (p.D64G) 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 191, causing the aspartic acid (D) at amino acid position 64 to be replaced by a glycine (G). 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

-0.46

BayesDel_noAF

Benign

-0.61

CADD

Benign

2.2

DANN

Benign

0.63

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.0079

LIST_S2

Benign

0.060

M_CAP

Benign

0.00071

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;D;N

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.064

Sift

Benign

0.32

Sift4G

Benign

0.43

Vest4

0.10

MVP

0.23

MPC

0.035

ClinPred

0.086

GERP RS

-2.0

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000046

dbscSNV1_RF

Benign

0.0020

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