Genetic Variant ZNF805:p.Val195Leu (chr19-57253402-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001023563.4(ZNF805):c.583G>C(p.Val195Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ZNF805
NM_001023563.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.85

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042479694).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001023563.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF805	NM_001023563.4	MANE Select	c.583G>C	p.Val195Leu	missense	Exon 4 of 4	NP_001018857.2
	ZNF805	NM_001145078.2		c.184G>C	p.Val62Leu	missense	Exon 3 of 3	NP_001138550.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF805	ENST00000414468.3	TSL:5 MANE Select	c.583G>C	p.Val195Leu	missense	Exon 4 of 4	ENSP00000412999.1
	ZNF805	ENST00000354309.4	TSL:5	c.184G>C	p.Val62Leu	missense	Exon 3 of 3	ENSP00000365414.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.10e-7

AC:

AN:

1408320

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

695698

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31860

American (AMR)

AF:

0.00

AC:

AN:

36346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25264

East Asian (EAS)

AF:

0.00

AC:

AN:

36490

South Asian (SAS)

AF:

0.00

AC:

AN:

80218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

9.23e-7

AC:

AN:

1083874

Other (OTH)

AF:

0.00

AC:

AN:

58450

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0020

(source)

DANN

Benign

0.097

DEOGEN2

Benign

0.0014

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.0065

M_CAP

Benign

0.0028

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.17

PhyloP100

-2.9

PrimateAI

Benign

0.26

PROVEAN

Benign

0.48

REVEL

Benign

0.015

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.019

MutPred

0.26

Loss of methylation at K192 (P = 0.0831)

MVP

0.043

MPC

0.24

ClinPred

0.036

GERP RS

-8.7

Varity_R

0.031

gMVP

0.018

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over