Variant 19-51944125-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001031721.4(ZNF613):c.242A>C(p.Lys81Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,524,984 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

ZNF613
NM_001031721.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.585

Variant links:

Genes affected

ZNF613 (HGNC:25827): (zinc finger protein 613) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF613 links:

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=0.029859453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF613	NM_001031721.4 linkuse as main transcript	c.242A>C	p.Lys81Thr	missense_variant	6/6	ENST00000293471.11	NP_001026891.2	Q6PF04-1
ZNF613	NM_024840.4 linkuse as main transcript	c.134A>C	p.Lys45Thr	missense_variant	6/6		NP_079116.2	Q6PF04-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF613	ENST00000293471.11 linkuse as main transcript	c.242A>C	p.Lys81Thr	missense_variant	6/6	1	NM_001031721.4	ENSP00000293471.5	Q6PF04-1
ZNF613	ENST00000391794.8 linkuse as main transcript	c.134A>C	p.Lys45Thr	missense_variant	6/6	2		ENSP00000375671.3	Q6PF04-2
ZNF613	ENST00000600853.1 linkuse as main transcript	c.242A>C	p.Lys81Thr	missense_variant	5/5	4		ENSP00000468850.1	M0QX19
ZNF613	ENST00000599683.5 linkuse as main transcript	c.134A>C	p.Lys45Thr	missense_variant	5/5	3		ENSP00000472455.1	M0R2C1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

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

GnomAD3 exomes

AF:

0.0000702

AC:

AN:

185126

Hom.:

AF XY:

0.0000806

AC XY:

AN XY:

99252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000826

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:

0.0000488

AC:

AN:

1372750

Hom.:

Cov.:

AF XY:

0.0000534

AC XY:

AN XY:

674180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00168

Gnomad4 SAS exome

AF:

0.0000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000177

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000384

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000495

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Feb 14, 2024

The c.242A>C (p.K81T) alteration is located in exon 6 (coding exon 4) of the ZNF613 gene. This alteration results from a A to C substitution at nucleotide position 242, causing the lysine (K) at amino acid position 81 to be replaced by a threonine (T). 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

0.096

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0061

T;.;.;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.0091

T;T;T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.030

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.73

N;.;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.3

N;N;.;.

REVEL

Benign

0.018

Sift

Benign

0.61

T;T;.;.

Sift4G

Benign

0.64

T;T;T;T

Polyphen

0.26

B;.;.;.

Vest4

0.17

MutPred

0.40

Loss of ubiquitination at K81 (P = 0.0155);.;.;Loss of ubiquitination at K81 (P = 0.0155);

MVP

0.34

MPC

0.11

ClinPred

0.021

GERP RS

2.3

Varity_R

0.081

gMVP

0.062

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over