chr19-53140666-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.2162G>A​(p.Arg721His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000258 in 1,602,820 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

ZNF347
NM_032584.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.89
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=0.027639002).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF347NM_032584.3 linkc.2162G>A p.Arg721His missense_variant Exon 5 of 5 ENST00000334197.12 NP_115973.2 Q96SE7-1
ZNF347NM_001172674.2 linkc.2165G>A p.Arg722His missense_variant Exon 5 of 5 NP_001166145.1 Q96SE7-2A0A024R4L7
ZNF347NM_001172675.2 linkc.2165G>A p.Arg722His 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.2162G>A p.Arg721His missense_variant Exon 5 of 5 1 NM_032584.3 ENSP00000334146.6 Q96SE7-1
ZNF347ENST00000452676.6 linkc.2165G>A p.Arg722His missense_variant Exon 5 of 5 2 ENSP00000405218.2 Q96SE7-2
ZNF347ENST00000601469.2 linkc.2165G>A p.Arg722His missense_variant Exon 5 of 5 2 ENSP00000471712.2 Q96SE7-2
ZNF347ENST00000601804.5 linkc.97+8015G>A intron_variant Intron 3 of 3 4 ENSP00000470590.1 M0QZJ6

Frequencies

GnomAD3 genomes
AF:
0.000224
AC:
32
AN:
142920
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000786
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000631
Gnomad SAS
AF:
0.000445
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000352
Gnomad OTH
AF:
0.000515
GnomAD3 exomes
AF:
0.000217
AC:
54
AN:
248746
Hom.:
0
AF XY:
0.000223
AC XY:
30
AN XY:
134518
show subpopulations
Gnomad AFR exome
AF:
0.000125
Gnomad AMR exome
AF:
0.0000588
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000444
Gnomad SAS exome
AF:
0.0000994
Gnomad FIN exome
AF:
0.0000927
Gnomad NFE exome
AF:
0.000310
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000257
AC:
375
AN:
1459766
Hom.:
0
Cov.:
31
AF XY:
0.000238
AC XY:
173
AN XY:
726170
show subpopulations
Gnomad4 AFR exome
AF:
0.0000899
Gnomad4 AMR exome
AF:
0.0000675
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000760
Gnomad4 SAS exome
AF:
0.0000349
Gnomad4 FIN exome
AF:
0.000112
Gnomad4 NFE exome
AF:
0.000305
Gnomad4 OTH exome
AF:
0.000282
GnomAD4 genome
AF:
0.000273
AC:
39
AN:
143054
Hom.:
1
Cov.:
33
AF XY:
0.000244
AC XY:
17
AN XY:
69564
show subpopulations
Gnomad4 AFR
AF:
0.000261
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000632
Gnomad4 SAS
AF:
0.000445
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000352
Gnomad4 OTH
AF:
0.000510
Alfa
AF:
0.000194
Hom.:
0
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000247
AC:
30
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 18, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2165G>A (p.R722H) 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 2165, causing the arginine (R) at amino acid position 722 to be replaced by a histidine (H). 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
0.13
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
5.5
DANN
Uncertain
0.97
DEOGEN2
Benign
0.041
T;.;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0067
N
LIST_S2
Benign
0.087
T;T;.
M_CAP
Benign
0.00082
T
MetaRNN
Benign
0.028
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;.;.
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.8
N;N;.
REVEL
Benign
0.024
Sift
Benign
0.073
T;T;.
Sift4G
Benign
0.48
T;T;T
Polyphen
0.035
B;.;.
Vest4
0.043
MVP
0.13
MPC
0.013
ClinPred
0.11
T
GERP RS
-5.2
Varity_R
0.022
gMVP
0.026

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: rs150489253; hg19: chr19-53643919; COSMIC: COSV100498114; COSMIC: COSV100498114; API