chr19-57211517-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_003417.5(ZNF264):ā€‹c.420C>Gā€‹(p.Phe140Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,962 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 Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

ZNF264
NM_003417.5 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.309
Variant links:
Genes affected
ZNF264 (HGNC:13057): (zinc finger protein 264) This gene encodes a zinc finger protein and belongs to the krueppel C2H2-type zinc-finger protein family. Zinc finger proteins are often localized in the nucleus, bind nucleic acids, and regulate transcription. [provided by RefSeq, Jan 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03598553).
BP6
Variant 19-57211517-C-G is Benign according to our data. Variant chr19-57211517-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2389353.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF264NM_003417.5 linkuse as main transcriptc.420C>G p.Phe140Leu missense_variant 4/4 ENST00000263095.10 NP_003408.1 O43296
ZNF264XM_047439724.1 linkuse as main transcriptc.420C>G p.Phe140Leu missense_variant 5/5 XP_047295680.1
ZNF264XM_011527522.3 linkuse as main transcriptc.324C>G p.Phe108Leu missense_variant 3/3 XP_011525824.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF264ENST00000263095.10 linkuse as main transcriptc.420C>G p.Phe140Leu missense_variant 4/42 NM_003417.5 ENSP00000263095.5 O43296
ZNF264ENST00000597447.5 linkuse as main transcriptc.*34C>G downstream_gene_variant 3 ENSP00000470587.1 M0QZJ4

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152076
Hom.:
0
Cov.:
32
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:
0.00000398
AC:
1
AN:
251352
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135850
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
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:
0.00000342
AC:
5
AN:
1461886
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152076
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74302
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:
0.0000282
Hom.:
0
Bravo
AF:
0.0000416

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsOct 14, 2021This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.10
DANN
Benign
0.23
DEOGEN2
Benign
0.0025
T;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.11
.;T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.036
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-2.0
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
1.8
N;N
REVEL
Benign
0.0090
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.012
MutPred
0.23
Loss of catalytic residue at F140 (P = 0.1358);Loss of catalytic residue at F140 (P = 0.1358);
MVP
0.055
MPC
0.065
ClinPred
0.046
T
GERP RS
-2.8
Varity_R
0.037
gMVP
0.040

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: rs1043828903; hg19: chr19-57722885; API