Variant 4-85805-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000610261.6(ZNF595):c.301A>C(p.Lys101Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,613,790 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 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

ZNF595
ENST00000610261.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.086161196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF595	NM_182524.4 linkuse as main transcript	c.301A>C	p.Lys101Gln	missense_variant	4/4	ENST00000610261.6	NP_872330.1	Q8IYB9
ZNF595	NM_001286052.2 linkuse as main transcript	c.205A>C	p.Lys69Gln	missense_variant	3/3		NP_001272981.1	Q8IYB9A0A075B7G4B4DU56
ZNF595	NM_001286053.2 linkuse as main transcript	c.-249A>C		5_prime_UTR_variant	2/2		NP_001272982.1	Q8IYB9A0A075B7G3B4DX79
ZNF595	NM_001286054.2 linkuse as main transcript	c.-249A>C		5_prime_UTR_variant	5/5		NP_001272983.1	Q8IYB9A0A075B7G3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF595	ENST00000610261.6 linkuse as main transcript	c.301A>C	p.Lys101Gln	missense_variant	4/4	1	NM_182524.4	ENSP00000477392.1	Q8IYB9
ZNF595	ENST00000609518.5 linkuse as main transcript	c.205A>C	p.Lys69Gln	missense_variant	3/3	2		ENSP00000476408.2	A0A075B7G4
ZNF595	ENST00000608255 linkuse as main transcript	c.-249A>C		5_prime_UTR_variant	2/2	2		ENSP00000476367.2	A0A075B7G3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000360

AC:

AN:

249820

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.0000645

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:

0.0000707

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000801

AC:

117

AN:

1461570

Hom.:

Cov.:

AF XY:

0.0000921

AC XY:

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000447

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:

0.000102

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000494

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000495

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

Jun 18, 2024

The c.301A>C (p.K101Q) alteration is located in exon 4 (coding exon 4) of the ZNF595 gene. This alteration results from a A to C substitution at nucleotide position 301, causing the lysine (K) at amino acid position 101 to be replaced by a glutamine (Q). 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

0.099

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.54

DEOGEN2

Benign

0.036

T;.

FATHMM_MKL

Benign

0.00019

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.086

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.0070

B;.

Vest4

0.070

MVP

0.19

GERP RS

-0.76

Varity_R

0.10

gMVP

0.056

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