19-52950010-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001202457.3(ZNF816):c.1765G>A(p.Gly589Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF816
NM_001202457.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56

Variant links:

Genes affected

ZNF816 (HGNC:26995): (zinc finger protein 816) 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 be integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF816 links:

ZNF816-ZNF321P (HGNC:38879): (ZNF816-ZNF321P readthrough) This locus represents naturally occurring read-through transcription between the zinc finger protein 816 (ZNF816) gene and the zinc finger protein 321 (ZNF321) pseudogene on chromosome 19. The read-through transcript encodes a KRAB domain-containing protein that shares sequence identity with the upstream gene product, but it contains a distinct C-terminus encoded by exon structure from the downstream pseudogene. [provided by RefSeq, Jan 2011]

ZNF816-ZNF321P links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2397027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF816	NM_001202457.3 link	c.1765G>A	p.Gly589Arg	missense_variant	Exon 4 of 4	ENST00000444460.7	NP_001189386.1	Q0VGE8A0A024R4J0
ZNF816	NM_001031665.4 link	c.1765G>A	p.Gly589Arg	missense_variant	Exon 5 of 5		NP_001026835.1	Q0VGE8A0A024R4J0
ZNF816	NM_001202456.3 link	c.1765G>A	p.Gly589Arg	missense_variant	Exon 4 of 4		NP_001189385.1	Q0VGE8A0A024R4J0
ZNF816-ZNF321P	NM_001202473.2 link	c.190+2741G>A		intron_variant	Intron 3 of 3		NP_001189402.1	Q8N8H1A0A0X1KG74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF816	ENST00000444460.7 link	c.1765G>A	p.Gly589Arg	missense_variant	Exon 4 of 4	1	NM_001202457.3	ENSP00000403266.2	Q0VGE8
ZNF816	ENST00000357666.8 link	c.1765G>A	p.Gly589Arg	missense_variant	Exon 5 of 5	1		ENSP00000350295.4	Q0VGE8
ZNF816-ZNF321P	ENST00000391777.3 link	c.190+2741G>A		intron_variant	Intron 3 of 3	2		ENSP00000375656.3	A0A0X1KG74

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251204

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461736

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1765G>A (p.G589R) alteration is located in exon 5 (coding exon 3) of the ZNF816 gene. This alteration results from a G to A substitution at nucleotide position 1765, causing the glycine (G) at amino acid position 589 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

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

T;T

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.088

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.25

.;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-6.5

D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

1.0

D;D

Vest4

0.14

MutPred

0.40

Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);

MVP

0.36

MPC

0.48

ClinPred

0.98

GERP RS

1.8

Varity_R

0.41

gMVP

0.017

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