Genetic Variant ZNF71:p.Glu185Lys (chr19-56621660-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001370215.1(ZNF71):c.553G>A(p.Glu185Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ZNF71
NM_001370215.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.329

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038579136).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370215.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF71	NM_001370215.1	MANE Select	c.553G>A	p.Glu185Lys	missense	Exon 4 of 4	NP_001357144.1	M0R0C0
ZNF71	NM_001370214.1		c.373G>A	p.Glu125Lys	missense	Exon 3 of 3	NP_001357143.1	Q9NQZ8
ZNF71	NM_021216.5		c.373G>A	p.Glu125Lys	missense	Exon 3 of 3	NP_067039.1	Q9NQZ8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF71	ENST00000599599.7	TSL:2 MANE Select	c.553G>A	p.Glu185Lys	missense	Exon 4 of 4	ENSP00000471138.2	M0R0C0
ZNF71	ENST00000328070.10	TSL:1	c.373G>A	p.Glu125Lys	missense	Exon 3 of 3	ENSP00000328245.5	Q9NQZ8
ENSG00000293626	ENST00000716550.1		n.160+7722G>A		intron	N/A	ENSP00000520562.1	A0ABB0MV33

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251152

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461684

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111876

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.8

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.16

M_CAP

Benign

0.0041

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.63

PhyloP100

-0.33

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.19

REVEL

Benign

0.013

Sift

Uncertain

0.015

Sift4G

Uncertain

0.017

Polyphen

0.0010

Vest4

0.13

MVP

0.014

MPC

0.41

ClinPred

0.065

GERP RS

-1.2

Varity_R

0.036

gMVP

0.032

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over