Variant 4-112558160-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018392.5(ZGRF1):c.5110G>A(p.Val1704Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,604,612 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 3 hom. )

Consequence

ZGRF1
NM_018392.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.622

Variant links:

Genes affected

ZGRF1 (HGNC:25654): (zinc finger GRF-type containing 1) The encoded protein contains GRF zinc finger (zf-GRF) and transmembrane domains. GRF zinc fingers are found in a number of DNA-binding proteins. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

ZGRF1 links:

ZGRF1 (HGNC:):

ZGRF1 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=0.019569367).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZGRF1	NM_018392.5 linkuse as main transcript	c.5110G>A	p.Val1704Ile	missense_variant	20/28	ENST00000505019.6	NP_060862.3	Q86YA3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZGRF1	ENST00000505019.6 linkuse as main transcript	c.5110G>A	p.Val1704Ile	missense_variant	20/28	5	NM_018392.5	ENSP00000424737.1		Q86YA3-1

Frequencies

GnomAD3 genomes

AF:

0.000717

AC:

109

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000899

AC:

217

AN:

241246

Hom.:

AF XY:

0.000996

AC XY:

130

AN XY:

130570

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.0000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00167

Gnomad NFE exome

AF:

0.00153

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.00110

AC:

1600

AN:

1452514

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

796

AN XY:

722360

show subpopulations

Gnomad4 AFR exome

AF:

0.000183

Gnomad4 AMR exome

AF:

0.0000474

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00131

Gnomad4 OTH exome

AF:

0.000766

GnomAD4 genome

AF:

0.000717

AC:

109

AN:

152098

Hom.:

Cov.:

AF XY:

0.000660

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.00135

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000650

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000791

AC:

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

Jan 18, 2022

The c.5110G>A (p.V1704I) alteration is located in exon 20 (coding exon 19) of the ZGRF1 gene. This alteration results from a G to A substitution at nucleotide position 5110, causing the valine (V) at amino acid position 1704 to be replaced by an isoleucine (I). 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

0.083

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0080

T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.70

T;.

M_CAP

Benign

0.051

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.25

N;N

PROVEAN

Benign

-0.19

.;N

REVEL

Benign

0.23

Sift

Benign

0.31

.;T

Sift4G

Benign

0.48

T;T

Vest4

0.36

MVP

0.38

MPC

0.17

ClinPred

0.062

GERP RS

4.0

Varity_R

0.032

gMVP

0.083

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