15-84782967-T-C

Variant names:

• chr15-84782967-T-C
• NM_014630.3:c.292T>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.693

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]

ACMG classification

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 rank	MANE	Protein	UniProt
ZNF592	NM_014630.3	c.292T>C	p.Ser98Pro	missense_variant	Exon 4 of 11	ENST00000560079.7	NP_055445.2
ZNF592	XM_005254996.4	c.292T>C	p.Ser98Pro	missense_variant	Exon 3 of 10		XP_005255053.1
ZNF592	XM_011522246.3	c.292T>C	p.Ser98Pro	missense_variant	Exon 4 of 11		XP_011520548.1
ZNF592	XM_011522247.3	c.292T>C	p.Ser98Pro	missense_variant	Exon 3 of 10		XP_011520549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF592	ENST00000560079.7	c.292T>C	p.Ser98Pro	missense_variant	Exon 4 of 11	1	NM_014630.3	ENSP00000452877.2
ZNF592	ENST00000559607.1	n.292T>C		non_coding_transcript_exon_variant	Exon 2 of 9	1		ENSP00000453491.1
ZNF592	ENST00000299927.4	c.292T>C	p.Ser98Pro	missense_variant	Exon 1 of 8	2		ENSP00000299927.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

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.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 04, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.88
DEOGEN2	Benign	0.013	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.61	.;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.020	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.35	T
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	T
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.

Other links and lift over

hg19: chr15-85326198;