Variant 15-84782967-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014630.3(ZNF592):c.292T>C(p.Ser98Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF592
NM_014630.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.693

Variant links:

Genes affected

ZNF592 (HGNC:28986): (zinc finger protein 592) This gene is thought to play a role in a complex developmental pathway and the regulation of genes involved in cerebellar development. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia. [provided by RefSeq, Jan 2011]

ZNF592 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020450413).

BP6

Variant 15-84782967-T-C is Benign according to our data. Variant chr15-84782967-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2616442.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF592	NM_014630.3 linkuse as main transcript	c.292T>C	p.Ser98Pro	missense_variant	4/11	ENST00000560079.7	NP_055445.2
ZNF592	XM_005254996.4 linkuse as main transcript	c.292T>C	p.Ser98Pro	missense_variant	3/10		XP_005255053.1
ZNF592	XM_011522246.3 linkuse as main transcript	c.292T>C	p.Ser98Pro	missense_variant	4/11		XP_011520548.1
ZNF592	XM_011522247.3 linkuse as main transcript	c.292T>C	p.Ser98Pro	missense_variant	3/10		XP_011520549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF592	ENST00000560079.7 linkuse as main transcript	c.292T>C	p.Ser98Pro	missense_variant	4/11	1	NM_014630.3	ENSP00000452877	P1
ZNF592	ENST00000559607.1 linkuse as main transcript	c.292T>C	p.Ser98Pro	missense_variant, NMD_transcript_variant	2/9	1		ENSP00000453491
ZNF592	ENST00000299927.4 linkuse as main transcript	c.292T>C	p.Ser98Pro	missense_variant	1/8	2		ENSP00000299927	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.61

.;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.060

N;N

REVEL

Benign

0.072

Sift

Benign

0.33

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.0

B;B

Vest4

0.21

MutPred

0.11

Loss of phosphorylation at S98 (P = 0.0272);Loss of phosphorylation at S98 (P = 0.0272);

MVP

0.043

MPC

0.33

ClinPred

0.069

GERP RS

-1.6

Varity_R

0.13

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over