chr19-57253079-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001023563.4(ZNF805):ā€‹c.260A>Gā€‹(p.Lys87Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000763 in 1,441,022 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000078 ( 0 hom. )

Consequence

ZNF805
NM_001023563.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.607
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]

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=0.04518065).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF805NM_001023563.4 linkuse as main transcriptc.260A>G p.Lys87Arg missense_variant 4/4 ENST00000414468.3
ZNF805NM_001145078.2 linkuse as main transcriptc.-140A>G 5_prime_UTR_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF805ENST00000414468.3 linkuse as main transcriptc.260A>G p.Lys87Arg missense_variant 4/45 NM_001023563.4 P1Q5CZA5-1
ZNF805ENST00000354309.4 linkuse as main transcriptc.-140A>G 5_prime_UTR_variant 3/35 Q5CZA5-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000776
AC:
10
AN:
1288826
Hom.:
0
Cov.:
29
AF XY:
0.00000641
AC XY:
4
AN XY:
623950
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000973
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000333
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000857
AC:
1

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 submitterclinical testingAmbry GeneticsMay 30, 2023The c.260A>G (p.K87R) alteration is located in exon 4 (coding exon 4) of the ZNF805 gene. This alteration results from a A to G substitution at nucleotide position 260, causing the lysine (K) at amino acid position 87 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
Benign
0.066
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
12
DANN
Benign
0.91
DEOGEN2
Benign
0.0054
T
Eigen
Benign
-0.93
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.032
T
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.045
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.010
Sift
Benign
0.50
T
Sift4G
Benign
0.43
T
Polyphen
0.19
B
Vest4
0.050
MVP
0.31
MPC
0.20
ClinPred
0.063
T
GERP RS
0.70
Varity_R
0.054
gMVP
0.031

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.

Other links and lift over

dbSNP: rs771622195; hg19: chr19-57764447; API