19-52949909-C-G

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.1866G>C(p.Lys622Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ZNF816
NM_001202457.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.25

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:

Genome browser will be placed here

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=0.119761735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF816	NM_001202457.3 link	c.1866G>C	p.Lys622Asn	missense_variant	Exon 4 of 4	ENST00000444460.7	NP_001189386.1	Q0VGE8A0A024R4J0
ZNF816	NM_001031665.4 link	c.1866G>C	p.Lys622Asn	missense_variant	Exon 5 of 5		NP_001026835.1	Q0VGE8A0A024R4J0
ZNF816	NM_001202456.3 link	c.1866G>C	p.Lys622Asn	missense_variant	Exon 4 of 4		NP_001189385.1	Q0VGE8A0A024R4J0
ZNF816-ZNF321P	NM_001202473.2 link	c.190+2842G>C		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.1866G>C	p.Lys622Asn	missense_variant	Exon 4 of 4	1	NM_001202457.3	ENSP00000403266.2	Q0VGE8
ZNF816	ENST00000357666.8 link	c.1866G>C	p.Lys622Asn	missense_variant	Exon 5 of 5	1		ENSP00000350295.4	Q0VGE8
ZNF816-ZNF321P	ENST00000391777.3 link	c.190+2842G>C		intron_variant	Intron 3 of 3	2		ENSP00000375656.3	A0A0X1KG74

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

251072

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000289

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:

0.0000151

AC:

AN:

1461590

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

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:

0.000298

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.000169

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1866G>C (p.K622N) alteration is located in exon 5 (coding exon 3) of the ZNF816 gene. This alteration results from a G to C substitution at nucleotide position 1866, causing the lysine (K) at amino acid position 622 to be replaced by an asparagine (N). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.13

.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.063

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

1.0

D;D

Vest4

0.059

MutPred

0.37

Loss of methylation at K622 (P = 2e-04);Loss of methylation at K622 (P = 2e-04);

MVP

0.14

MPC

0.48

ClinPred

0.42

GERP RS

0.62

Varity_R

0.21

gMVP

0.010

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