19-56621433-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370215.1(ZNF71):​c.326G>C​(p.Arg109Pro) 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 1,613,710 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R109W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ZNF71
NM_001370215.1 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.789

Publications

0 publications found
Variant links:
Genes affected
ZNF71 (HGNC:13141): (zinc finger protein 71) Predicted to enable DNA-binding transcription activator 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]
ZIM2-AS1 (HGNC:51304): (ZIM2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.079304606).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF71NM_001370215.1 linkc.326G>C p.Arg109Pro missense_variant Exon 4 of 4 ENST00000599599.7 NP_001357144.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF71ENST00000599599.7 linkc.326G>C p.Arg109Pro missense_variant Exon 4 of 4 2 NM_001370215.1 ENSP00000471138.2 M0R0C0
ENSG00000293626ENST00000716550.1 linkn.160+7495G>C intron_variant Intron 3 of 5 ENSP00000520562.1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152146
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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
GnomAD2 exomes
AF:
0.0000120
AC:
3
AN:
250320
AF XY:
0.00000739
show subpopulations
Gnomad AFR exome
AF:
0.0000619
Gnomad AMR exome
AF:
0.0000581
Gnomad ASJ exome
AF:
0.00
Gnomad EAS 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:
0.00000547
AC:
8
AN:
1461564
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727076
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33472
American (AMR)
AF:
0.0000448
AC:
2
AN:
44666
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26122
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39692
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86226
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53392
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000450
AC:
5
AN:
1111856
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60370
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.469
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
AF:
0.0000263
AC:
4
AN:
152146
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74330
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41442
American (AMR)
AF:
0.000131
AC:
2
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5176
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68016
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
0.19
DANN
Benign
0.82
DEOGEN2
Benign
0.037
.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.069
N
LIST_S2
Benign
0.15
T;T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.079
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.63
.;N
PhyloP100
-0.79
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.1
.;N
REVEL
Benign
0.084
Sift
Benign
0.21
.;T
Sift4G
Benign
0.18
.;T
Polyphen
0.41
.;B
Vest4
0.19
MutPred
0.25
.;Gain of catalytic residue at P48 (P = 0.0155);
MVP
0.014
MPC
0.57
ClinPred
0.045
T
GERP RS
-5.8
Varity_R
0.11
gMVP
0.057
Mutation Taster
=99/1
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs200215840; hg19: chr19-57132801; COSMIC: COSV60150312; API