Variant 4-85997-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182524.4(ZNF595):c.493A>G(p.Ile165Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000259 in 1,608,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

ZNF595
NM_182524.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.35

Variant links:

Genes affected

ZNF595 (HGNC:27196): (zinc finger protein 595) This gene encodes a protein belonging to the Cys2His2 zinc finger protein family, whose members function as transcription factors that can regulate a broad variety of developmental and cellular processes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Oct 2013]

ZNF595 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049398303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF595	NM_182524.4 linkuse as main transcript	c.493A>G	p.Ile165Val	missense_variant	4/4	ENST00000610261.6	NP_872330.1
ZNF595	NM_001286052.2 linkuse as main transcript	c.397A>G	p.Ile133Val	missense_variant	3/3		NP_001272981.1
ZNF595	NM_001286053.2 linkuse as main transcript	c.-57A>G		5_prime_UTR_variant	2/2		NP_001272982.1
ZNF595	NM_001286054.2 linkuse as main transcript	c.-57A>G		5_prime_UTR_variant	5/5		NP_001272983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF595	ENST00000610261.6 linkuse as main transcript	c.493A>G	p.Ile165Val	missense_variant	4/4	1	NM_182524.4	ENSP00000477392	P1
ZNF595	ENST00000609518.5 linkuse as main transcript	c.397A>G	p.Ile133Val	missense_variant	3/3	2		ENSP00000476408
ZNF595	ENST00000608255.2 linkuse as main transcript	c.-57A>G		5_prime_UTR_variant	2/2	2		ENSP00000476367

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000850

AC:

AN:

235266

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

127388

show subpopulations

Gnomad AFR exome

AF:

0.0000687

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000172

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.000270

AC:

393

AN:

1455774

Hom.:

Cov.:

AF XY:

0.000246

AC XY:

178

AN XY:

723666

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000342

Gnomad4 OTH exome

AF:

0.0000997

GnomAD4 genome

AF:

0.000151

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000173

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000247

AC:

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.0000413

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 26, 2022

The c.493A>G (p.I165V) alteration is located in exon 4 (coding exon 4) of the ZNF595 gene. This alteration results from a A to G substitution at nucleotide position 493, causing the isoleucine (I) at amino acid position 165 to be replaced by a valine (V). 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

0.091

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.6

DANN

Benign

0.90

DEOGEN2

Benign

0.011

T;.

FATHMM_MKL

Benign

0.00057

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

0.049

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0

B;.

Vest4

0.019

MVP

0.16

GERP RS

1.1

Varity_R

0.031

gMVP

0.0027

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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