chr15-84798628-G-C

Variant names:

• chr15-84798628-G-C
• rs8182086
• NM_014630.3:c.2777G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014630.3(ZNF592):​c.2777G>C​(p.Ser926Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S926N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF592 NM_014630.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.961
• Publications: 46 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14089844).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014630.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF592	NM_014630.3	MANE Select	c.2777G>C	p.Ser926Thr	missense	Exon 8 of 11	NP_055445.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF592	ENST00000560079.7	TSL:1 MANE Select	c.2777G>C	p.Ser926Thr	missense	Exon 8 of 11	ENSP00000452877.2
	ZNF592	ENST00000559607.1	TSL:1	n.*189G>C		non_coding_transcript_exon	Exon 6 of 9	ENSP00000453491.1
	ZNF592	ENST00000559607.1	TSL:1	n.*189G>C		3_prime_UTR	Exon 6 of 9	ENSP00000453491.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 15267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	-0.047	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.96
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.12
Sift	Benign	0.24	T
Sift4G	Uncertain	0.046	D
Polyphen		0.89	P
Vest4		0.16
MutPred		0.17		Loss of phosphorylation at S926 (P = 0.067)
MVP		0.14
MPC		0.89
ClinPred		0.64	D
GERP RS		4.8
Varity_R		0.13
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8182086; hg19: chr15-85341859;