Variant 8-144837441-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003416.4(ZNF7):c.181G>A(p.Glu61Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,138 control chromosomes in the GnomAD database, including 2 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 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000041 ( 2 hom. )

Consequence

ZNF7
NM_003416.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.388

Variant links:

Genes affected

ZNF7 (HGNC:13139): (zinc finger protein 7) 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 integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024157852).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF7	NM_003416.4 linkuse as main transcript	c.181G>A	p.Glu61Lys	missense_variant	4/5	ENST00000532777.6	NP_003407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF7	ENST00000532777.6 linkuse as main transcript	c.181G>A	p.Glu61Lys	missense_variant	4/5	1	NM_003416.4	ENSP00000432641	P4	P17097-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152256

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:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000955

AC:

AN:

251300

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000411

AC:

AN:

1460882

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

726654

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:

0.000626

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.000157

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

Jun 18, 2021

The c.181G>A (p.E61K) alteration is located in exon 4 (coding exon 3) of the ZNF7 gene. This alteration results from a G to A substitution at nucleotide position 181, causing the glutamic acid (E) at amino acid position 61 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

0.12

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0093

T;.;.;T;.;T;T;T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.072

T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.024

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

.;.;N;.;.;.;.;N;.

MutationTaster

Benign

1.0

D;N;N;N;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.81

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.048

Sift

Benign

0.083

T;T;T;T;T;T;T;T;T

Sift4G

Uncertain

0.028

D;T;T;T;T;T;T;T;T

Polyphen

0.018, 0.043

.;.;.;.;.;.;.;B;B

Vest4

0.23, 0.23, 0.22, 0.25, 0.23, 0.25

MutPred

0.48

Gain of ubiquitination at E61 (P = 0.0185);.;Gain of ubiquitination at E61 (P = 0.0185);.;.;.;.;Gain of ubiquitination at E61 (P = 0.0185);Gain of ubiquitination at E61 (P = 0.0185);

MVP

0.41

MPC

0.088

ClinPred

0.073

GERP RS

2.1

Varity_R

0.049

gMVP

0.11

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.

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