Variant 5-122152585-T-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 ENST00000296600.5(ZNF474):c.595T>C(p.Ser199Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,614,096 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0099 ( 32 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 24 hom. )

Consequence

ZNF474
ENST00000296600.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.722

Variant links:

Genes affected

ZNF474 (HGNC:23245): (zinc finger protein 474) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZNF474 links:

ENSG00000250803 (HGNC:53564): (zinc finger protein 475)

ENSG00000250803 links:

ENSG00000247311 (HGNC:):

ENSG00000247311 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030279458).

BP6

Variant 5-122152585-T-C is Benign according to our data. Variant chr5-122152585-T-C is described in ClinVar as [Benign]. Clinvar id is 784059.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00986 (1500/152204) while in subpopulation AFR AF= 0.0336 (1396/41528). AF 95% confidence interval is 0.0321. There are 32 homozygotes in gnomad4. There are 719 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF474	NM_207317.3 linkuse as main transcript	c.595T>C	p.Ser199Pro	missense_variant	2/2	ENST00000296600.5	NP_997200.1	Q6S9Z5
ZNF474-AS1	XR_007058915.1 linkuse as main transcript	n.272-1982A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF474	ENST00000296600.5 linkuse as main transcript	c.595T>C	p.Ser199Pro	missense_variant	2/2	1	NM_207317.3	ENSP00000296600.4		Q6S9Z5

Frequencies

GnomAD3 genomes

AF:

0.00984

AC:

1497

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0336

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00273

AC:

686

AN:

251246

Hom.:

AF XY:

0.00203

AC XY:

276

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.0336

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00113

AC:

1652

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

740

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0340

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.00257

GnomAD4 genome

AF:

0.00986

AC:

1500

AN:

152204

Hom.:

Cov.:

AF XY:

0.00966

AC XY:

719

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0336

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00182

Hom.:

Bravo

AF:

0.0118

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0334

AC:

147

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00322

AC:

391

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.090

DANN

Benign

0.69

DEOGEN2

Benign

0.00080

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.25

REVEL

Benign

0.12

Sift

Benign

0.32

Sift4G

Benign

0.31

Polyphen

0.0010

Vest4

0.028

MVP

0.014

MPC

0.0035

ClinPred

0.0093

GERP RS

-0.95

Varity_R

0.058

gMVP

0.053

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