5-43175100-T-G

Variant summary

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

The NM_001330707.2(ZNF131):ā€‹c.1839T>Gā€‹(p.Asn613Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00011 ( 0 hom., cov: 32)
Exomes š‘“: 0.000012 ( 0 hom. )

Consequence

ZNF131
NM_001330707.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.973
Variant links:
Genes affected
ZNF131 (HGNC:12915): (zinc finger protein 131) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription repressor activity, RNA polymerase II-specific; and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Located in intermediate filament cytoskeleton and nucleoplasm. [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=0.022148997).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF131NM_001330707.2 linkuse as main transcriptc.1839T>G p.Asn613Lys missense_variant 7/7 ENST00000682664.1 NP_001317636.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF131ENST00000682664.1 linkuse as main transcriptc.1839T>G p.Asn613Lys missense_variant 7/7 NM_001330707.2 ENSP00000507111 P1P52739-1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000410
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:
0.0000321
AC:
8
AN:
248872
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135128
show subpopulations
Gnomad AFR exome
AF:
0.000517
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:
0.0000116
AC:
17
AN:
1461738
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727166
show subpopulations
Gnomad4 AFR exome
AF:
0.000448
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152278
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.000409
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:
0.0000278
Hom.:
0
Bravo
AF:
0.000128
ESP6500AA
AF:
0.000790
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000579
AC:
7

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 GeneticsJun 24, 2022The c.1737T>G (p.N579K) alteration is located in exon 8 (coding exon 7) of the ZNF131 gene. This alteration results from a T to G substitution at nucleotide position 1737, causing the asparagine (N) at amino acid position 579 to be replaced by a lysine (K). 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
0.076
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
0.80
DANN
Benign
0.93
DEOGEN2
Benign
0.0083
T;.;.;.
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.72
T;.;.;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.022
T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.97
L;.;.;.
MutationTaster
Benign
1.0
D;N;N;N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.53
N;N;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.014
D;D;D;D
Sift4G
Benign
0.33
T;T;T;T
Polyphen
0.0080
B;B;B;B
Vest4
0.068
MutPred
0.14
Gain of ubiquitination at N613 (P = 0.0011);.;.;.;
MVP
0.42
MPC
0.50
ClinPred
0.0067
T
GERP RS
2.0
Varity_R
0.056
gMVP
0.090

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: rs201916814; hg19: chr5-43175202; API