Variant 19-57253281-G-A 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_001023563.4(ZNF805):c.462G>A(p.Met154Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000793 in 1,564,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00082 ( 0 hom. )

Consequence

ZNF805
NM_001023563.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.730

Variant links:

Genes affected

ZNF805 (HGNC:23272): (zinc finger protein 805) 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF805 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=0.015437335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF805	NM_001023563.4 linkuse as main transcript	c.462G>A	p.Met154Ile	missense_variant	4/4	ENST00000414468.3	NP_001018857.2
ZNF805	NM_001145078.2 linkuse as main transcript	c.63G>A	p.Met21Ile	missense_variant	3/3		NP_001138550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF805	ENST00000414468.3 linkuse as main transcript	c.462G>A	p.Met154Ile	missense_variant	4/4	5	NM_001023563.4	ENSP00000412999	P1	Q5CZA5-1
ZNF805	ENST00000354309.4 linkuse as main transcript	c.63G>A	p.Met21Ile	missense_variant	3/3	5		ENSP00000365414		Q5CZA5-2

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.000882

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000503

AC:

AN:

177068

Hom.:

AF XY:

0.000550

AC XY:

AN XY:

94476

show subpopulations

Gnomad AFR exome

AF:

0.000299

Gnomad AMR exome

AF:

0.000388

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000117

Gnomad NFE exome

AF:

0.000953

Gnomad OTH exome

AF:

0.000639

GnomAD4 exome

AF:

0.000825

AC:

1165

AN:

1412340

Hom.:

Cov.:

AF XY:

0.000785

AC XY:

548

AN XY:

697974

show subpopulations

Gnomad4 AFR exome

AF:

0.0000627

Gnomad4 AMR exome

AF:

0.000381

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000790

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.000700

GnomAD4 genome

AF:

0.000493

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000621

Hom.:

Bravo

AF:

0.000529

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.000325

AC:

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

Aug 02, 2021

The c.462G>A (p.M154I) alteration is located in exon 4 (coding exon 4) of the ZNF805 gene. This alteration results from a G to A substitution at nucleotide position 462, causing the methionine (M) at amino acid position 154 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.3

DANN

Benign

0.52

DEOGEN2

Benign

0.0058

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.052

T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.7

.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.45

N;N

REVEL

Benign

0.043

Sift

Benign

0.19

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.0010

.;B

Vest4

0.081

MutPred

0.22

.;Gain of methylation at K153 (P = 0.0223);

MVP

0.17

MPC

0.27

ClinPred

0.0011

GERP RS

-5.2

Varity_R

0.069

gMVP

0.11

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