Variant 19-56621309-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001370215.1(ZNF71):c.202A>G(p.Asn68Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,522,572 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000099 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 1 hom. )

Consequence

ZNF71
NM_001370215.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.278

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]

ZNF71 links:

ZIM2-AS1 (HGNC:):

ZIM2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021836072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF71	NM_001370215.1 linkuse as main transcript	c.202A>G	p.Asn68Asp	missense_variant	4/4	ENST00000599599.7	NP_001357144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF71	ENST00000599599.7 linkuse as main transcript	c.202A>G	p.Asn68Asp	missense_variant	4/4	2	NM_001370215.1	ENSP00000471138.2	M0R0C0
ZNF71	ENST00000328070.10 linkuse as main transcript	c.22A>G	p.Asn8Asp	missense_variant	3/3	1		ENSP00000328245.5	Q9NQZ8
ZIM2-AS1	ENST00000650950.1 linkuse as main transcript	n.201+19718A>G		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

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:

0.000478

GnomAD3 exomes

AF:

0.0000554

AC:

AN:

180396

Hom.:

AF XY:

0.0000315

AC XY:

AN XY:

95198

show subpopulations

Gnomad AFR exome

AF:

0.000588

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:

0.000243

GnomAD4 exome

AF:

0.0000379

AC:

AN:

1370360

Hom.:

Cov.:

AF XY:

0.0000357

AC XY:

AN XY:

671992

show subpopulations

Gnomad4 AFR exome

AF:

0.000726

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000141

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.35e-7

Gnomad4 OTH exome

AF:

0.000444

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000337

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:

0.000473

Alfa

AF:

0.0000222

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000415

AC:

Asia WGS

AF:

0.00144

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

Aug 20, 2024

The c.22A>G (p.N8D) alteration is located in exon 3 (coding exon 1) of the ZNF71 gene. This alteration results from a A to G substitution at nucleotide position 22, causing the asparagine (N) at amino acid position 8 to be replaced by an aspartic acid (D). 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

0.074

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.5

DANN

Benign

0.54

DEOGEN2

Benign

0.025

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00065

LIST_S2

Benign

0.057

T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.69

.;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.060

.;N

REVEL

Benign

0.026

Sift

Benign

0.49

.;T

Sift4G

Benign

0.51

.;T

Polyphen

0.0

.;B

Vest4

0.085

MVP

0.030

MPC

0.42

ClinPred

0.0066

GERP RS

2.4

Varity_R

0.038

gMVP

0.0099

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