chr15-84783280-A-G

Position:

• chr15-84783280-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_014630.3(ZNF592):​c.605A>G​(p.Lys202Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF592 NM_014630.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.78

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 3 ACMG points.

• PM1: In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) (size 0) in uniprot entity ZN592_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26596326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF592	NM_014630.3	c.605A>G	p.Lys202Arg	missense_variant	4/11	ENST00000560079.7
ZNF592	XM_005254996.4	c.605A>G	p.Lys202Arg	missense_variant	3/10
ZNF592	XM_011522246.3	c.605A>G	p.Lys202Arg	missense_variant	4/11
ZNF592	XM_011522247.3	c.605A>G	p.Lys202Arg	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF592	ENST00000560079.7	c.605A>G	p.Lys202Arg	missense_variant	4/11	1	NM_014630.3	P1
ZNF592	ENST00000559607.1	c.605A>G	p.Lys202Arg	missense_variant, NMD_transcript_variant	2/9	1
ZNF592	ENST00000299927.4	c.605A>G	p.Lys202Arg	missense_variant	1/8	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.605A>G (p.K202R) alteration is located in exon 4 (coding exon 1) of the ZNF592 gene. This alteration results from a A to G substitution at nucleotide position 605, causing the lysine (K) at amino acid position 202 to be replaced by an arginine (R). 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	0.086
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Uncertain	-0.050	T
MutationAssessor	Benign	0.81	L;L
MutationTaster	Benign	0.95	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.73	N;N
REVEL	Benign	0.24
Sift	Uncertain	0.010	D;D
Sift4G	Benign	0.16	T;T
Polyphen		1.0	D;D
Vest4		0.37
MutPred		0.28		Loss of methylation at K202 (P = 8e-04);Loss of methylation at K202 (P = 8e-04);
MVP		0.16
MPC		0.84
ClinPred		0.84	D
GERP RS		5.9
Varity_R		0.11
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr15-85326511;