Variant 16-75166821-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_153688.4(ZFP1):c.67G>C(p.Glu23Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 1,614,154 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 20 hom. )

Consequence

ZFP1
NM_153688.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

ZFP1 (HGNC:23328): (ZFP1 zinc finger protein) This gene belongs to the zinc finger protein family. Some members of this family bind to DNA by zinc-mediated secondary structures called zinc fingers, and are involved in transcriptional regulation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ZFP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00496307).

BP6

Variant 16-75166821-G-C is Benign according to our data. Variant chr16-75166821-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2646869.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0033 (4831/1461860) while in subpopulation MID AF= 0.0224 (129/5766). AF 95% confidence interval is 0.0192. There are 20 homozygotes in gnomad4_exome. There are 2520 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFP1	NM_153688.4 linkuse as main transcript	c.67G>C	p.Glu23Gln	missense_variant	3/4	ENST00000570010.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP1	ENST00000570010.6 linkuse as main transcript	c.67G>C	p.Glu23Gln	missense_variant	3/4	2	NM_153688.4	P1	Q6P2D0-1

Frequencies

GnomAD3 genomes

AF:

0.00268

AC:

408

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00378

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00304

AC:

760

AN:

250120

Hom.:

AF XY:

0.00324

AC XY:

440

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.000322

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.00745

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00323

Gnomad FIN exome

AF:

0.00167

Gnomad NFE exome

AF:

0.00397

Gnomad OTH exome

AF:

0.00329

GnomAD4 exome

AF:

0.00330

AC:

4831

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00347

AC XY:

2520

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00221

Gnomad4 ASJ exome

AF:

0.00651

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00271

Gnomad4 FIN exome

AF:

0.00204

Gnomad4 NFE exome

AF:

0.00345

Gnomad4 OTH exome

AF:

0.00354

GnomAD4 genome

AF:

0.00269

AC:

410

AN:

152294

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

194

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00378

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00380

Hom.:

Bravo

AF:

0.00266

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000699

AC:

ESP6500EA

AF:

0.00373

AC:

ExAC

AF:

0.00340

AC:

412

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00362

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

ZFP1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.11

DEOGEN2

Benign

0.037

T;.;T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.0049

MetaRNN

Benign

0.0050

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

-0.73

N;.;N;.

MutationTaster

Benign

0.82

D;D;D;D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

1.1

N;N;N;N

REVEL

Benign

0.095

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.11

B;.;B;.

Vest4

0.47

MVP

0.13

ClinPred

0.016

GERP RS

3.5

Varity_R

0.12

gMVP

0.19

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