chr19-53140364-C-T

Variant summary

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

The NM_032584.3(ZNF347):​c.2464G>A​(p.Val822Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,596,806 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 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ZNF347
NM_032584.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.402
Variant links:
Genes affected
ZNF347 (HGNC:16447): (zinc finger protein 347) 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=0.0651786).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF347NM_032584.3 linkc.2464G>A p.Val822Met missense_variant Exon 5 of 5 ENST00000334197.12 NP_115973.2 Q96SE7-1
ZNF347NM_001172674.2 linkc.2467G>A p.Val823Met missense_variant Exon 5 of 5 NP_001166145.1 Q96SE7-2A0A024R4L7
ZNF347NM_001172675.2 linkc.2467G>A p.Val823Met missense_variant Exon 5 of 5 NP_001166146.1 Q96SE7-2A0A024R4L7A8K1S9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF347ENST00000334197.12 linkc.2464G>A p.Val822Met missense_variant Exon 5 of 5 1 NM_032584.3 ENSP00000334146.6 Q96SE7-1
ZNF347ENST00000452676.6 linkc.2467G>A p.Val823Met missense_variant Exon 5 of 5 2 ENSP00000405218.2 Q96SE7-2
ZNF347ENST00000601469.2 linkc.2467G>A p.Val823Met missense_variant Exon 5 of 5 2 ENSP00000471712.2 Q96SE7-2
ZNF347ENST00000601804.5 linkc.97+8317G>A intron_variant Intron 3 of 3 4 ENSP00000470590.1 M0QZJ6

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152202
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000115
AC:
27
AN:
234832
Hom.:
0
AF XY:
0.000103
AC XY:
13
AN XY:
126720
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000315
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000369
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000233
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000127
AC:
183
AN:
1444604
Hom.:
0
Cov.:
30
AF XY:
0.000107
AC XY:
77
AN XY:
717848
show subpopulations
Gnomad4 AFR exome
AF:
0.0000305
Gnomad4 AMR exome
AF:
0.0000240
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000121
Gnomad4 FIN exome
AF:
0.0000380
Gnomad4 NFE exome
AF:
0.000157
Gnomad4 OTH exome
AF:
0.0000671
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152202
Hom.:
0
Cov.:
33
AF XY:
0.0000673
AC XY:
5
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000165
Hom.:
0
Bravo
AF:
0.0000945
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000659
AC:
8

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 09, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2467G>A (p.V823M) alteration is located in exon 5 (coding exon 4) of the ZNF347 gene. This alteration results from a G to A substitution at nucleotide position 2467, causing the valine (V) at amino acid position 823 to be replaced by a methionine (M). 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
0.12
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
2.3
DANN
Benign
0.68
DEOGEN2
Benign
0.027
T;.;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.055
T;T;.
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.065
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;.;.
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.40
N;N;.
REVEL
Benign
0.067
Sift
Uncertain
0.0060
D;D;.
Sift4G
Benign
0.32
T;T;T
Polyphen
0.92
P;.;.
Vest4
0.078
MVP
0.27
MPC
0.022
ClinPred
0.038
T
GERP RS
-5.8
Varity_R
0.034
gMVP
0.0080

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: rs368225234; hg19: chr19-53643617; COSMIC: COSV61968618; COSMIC: COSV61968618; API