15-84804941-G-T

Variant names:

• chr15-84804941-G-T
• rs1719
• NM_014630.3:c.*2548G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014630.3(ZNF592):​c.*2548G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 152,230 control chromosomes in the GnomAD database, including 400 homozygotes. 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: 𝑓 0.064 (400 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF592 NM_014630.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF592	NM_014630.3	c.*2548G>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000560079.7	NP_055445.2
ZNF592	XM_005254996.4	c.*2548G>T		3_prime_UTR_variant	Exon 10 of 10		XP_005255053.1
ZNF592	XM_011522246.3	c.*2548G>T		3_prime_UTR_variant	Exon 11 of 11		XP_011520548.1
ZNF592	XM_011522247.3	c.*2548G>T		3_prime_UTR_variant	Exon 10 of 10		XP_011520549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF592	ENST00000560079.7	c.*2548G>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_014630.3	ENSP00000452877.2
ZNF592	ENST00000299927.4	c.*2548G>T		3_prime_UTR_variant	Exon 8 of 8	2		ENSP00000299927.3
ZNF592	ENST00000618477.1	n.*142G>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9751 AN: 152112 Hom.: 399 Cov.: 33

Gnomad AFR AF: 0.0926

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0609

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0650

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0641 AC: 9764 AN: 152230 Hom.: 400 Cov.: 33 AF XY: 0.0631 AC XY: 4696 AN XY: 74414

African (AFR) AF: 0.0927 AC: 3852 AN: 41538

American (AMR) AF: 0.0424 AC: 648 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 343 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5180

South Asian (SAS) AF: 0.0608 AC: 293 AN: 4822

European-Finnish (FIN) AF: 0.0461 AC: 488 AN: 10594

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0583 AC: 3963 AN: 68010

Other (OTH) AF: 0.0643 AC: 136 AN: 2114

Alfa AF: 0.0495 Hom.: 149

Bravo AF: 0.0640

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.55
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1719; hg19: chr15-85348172;