Variant 5-43161535-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001330707.2(ZNF131):c.658A>C(p.Lys220Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF131
NM_001330707.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.68

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]

ZNF131 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF131	NM_001330707.2 link	c.658A>C	p.Lys220Gln	missense_variant	5/7	ENST00000682664.1	NP_001317636.1	P52739-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF131	ENST00000682664.1 link	c.658A>C	p.Lys220Gln	missense_variant	5/7		NM_001330707.2	ENSP00000507111.1		P52739-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.658A>C (p.K220Q) alteration is located in exon 5 (coding exon 4) of the ZNF131 gene. This alteration results from a A to C substitution at nucleotide position 658, causing the lysine (K) at amino acid position 220 to be replaced by a glutamine (Q). 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

Uncertain

0.52

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;T;.;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D;.;.;D

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.60

D;D;D;D;D

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

2.0

.;M;M;M;M

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.46

N;N;N;N;N

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

D;T;T;T;T

Sift4G

Benign

0.17

T;D;T;T;T

Polyphen

0.44, 1.0

.;B;D;D;D

Vest4

0.50, 0.81, 0.70, 0.70

MutPred

0.62

Loss of ubiquitination at K220 (P = 0.0155);Loss of ubiquitination at K220 (P = 0.0155);Loss of ubiquitination at K220 (P = 0.0155);Loss of ubiquitination at K220 (P = 0.0155);Loss of ubiquitination at K220 (P = 0.0155);

MVP

0.81

MPC

1.3

ClinPred

0.85

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.31

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over