Genetic Variant ZNF71:p.Ser71Leu (chr19-56621319-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001370215.1(ZNF71):c.212C>T(p.Ser71Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000435 in 1,525,856 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

ZNF71
NM_001370215.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.99

Publications

4 publications found

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:

ENSG00000293626 (HGNC:):

ENSG00000293626 links:

ZIM2-AS1 (HGNC:51304): (ZIM2 antisense RNA 1)

ZIM2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004624784).

BP6

Variant 19-56621319-C-T is Benign according to our data. Variant chr19-56621319-C-T is described in ClinVar as [Benign]. Clinvar id is 777547.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF71	NM_001370215.1 link	c.212C>T	p.Ser71Leu	missense_variant	Exon 4 of 4	ENST00000599599.7	NP_001357144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF71	ENST00000599599.7 link	c.212C>T	p.Ser71Leu	missense_variant	Exon 4 of 4	2	NM_001370215.1	ENSP00000471138.2		M0R0C0
ENSG00000293626	ENST00000716550.1 link	n.160+7381C>T		intron_variant	Intron 3 of 5			ENSP00000520562.1

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

360

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00825

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000826

AC:

151

AN:

182884

AF XY:

0.000641

show subpopulations

Gnomad AFR exome

AF:

0.00848

Gnomad AMR exome

AF:

0.000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000621

Gnomad FIN exome

AF:

0.0000577

Gnomad NFE exome

AF:

0.0000675

Gnomad OTH exome

AF:

0.000238

GnomAD4 exome

AF:

0.000218

AC:

300

AN:

1373560

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

130

AN XY:

673978

show subpopulations

African (AFR)

AF:

0.00723

AC:

220

AN:

30418

American (AMR)

AF:

0.000332

AC:

AN:

30090

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20290

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38922

South Asian (SAS)

AF:

0.000225

AC:

AN:

71260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5326

European-Non Finnish (NFE)

AF:

0.0000280

AC:

AN:

1070588

Other (OTH)

AF:

0.000407

AC:

AN:

56502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00238

AC:

363

AN:

152296

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00830

AC:

345

AN:

41570

American (AMR)

AF:

0.000457

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68030

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000999

Hom.:

Bravo

AF:

0.00243

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000844

AC:

102

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.014

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.042

.;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.016

T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.90

.;L

PhyloP100

-2.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.55

.;N

REVEL

Benign

0.0060

Sift

Benign

0.16

.;T

Sift4G

Benign

0.23

.;T

Polyphen

0.0

.;B

Vest4

0.082

MVP

0.014

MPC

0.33

ClinPred

0.0032

GERP RS

-5.7

Varity_R

0.021

gMVP

0.023

Mutation Taster

=100/0

polymorphism

(source)

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

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chr19-56621319-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over