15-84798469-G-T

Position:

• chr15-84798469-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014630.3(ZNF592):​c.2731G>T​(p.Val911Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: ZNF592 NM_014630.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89

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 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=0.194502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF592	NM_014630.3	c.2731G>T	p.Val911Phe	missense_variant	7/11	ENST00000560079.7	NP_055445.2
ZNF592	XM_005254996.4	c.2731G>T	p.Val911Phe	missense_variant	6/10		XP_005255053.1
ZNF592	XM_011522246.3	c.2731G>T	p.Val911Phe	missense_variant	7/11		XP_011520548.1
ZNF592	XM_011522247.3	c.2731G>T	p.Val911Phe	missense_variant	6/10		XP_011520549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF592	ENST00000560079.7	c.2731G>T	p.Val911Phe	missense_variant	7/11	1	NM_014630.3	ENSP00000452877.2
ZNF592	ENST00000559607.1	n.*143G>T		non_coding_transcript_exon_variant	5/9	1		ENSP00000453491.1
ZNF592	ENST00000559607.1	n.*143G>T		3_prime_UTR_variant	5/9	1		ENSP00000453491.1
ZNF592	ENST00000299927.4	c.2731G>T	p.Val911Phe	missense_variant	4/8	2		ENSP00000299927.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461650 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727074

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: 0.00000989

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	T;T
Eigen	Benign	-0.056
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.85	.;D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.090	N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.96	N;N
REVEL	Benign	0.13
Sift	Benign	0.27	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.36	B;B
Vest4		0.43
MutPred		0.30		Loss of ubiquitination at K912 (P = 0.1139);Loss of ubiquitination at K912 (P = 0.1139);
MVP		0.28
MPC		1.1
ClinPred		0.32	T
GERP RS		5.6
Varity_R		0.23
gMVP		0.63

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

Other links and lift over

dbSNP: rs1211858750; hg19: chr15-85341700;