rs366860

Positions:

• chr20-46512761-A-C
• chr20-46512761-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001353824.2(ZNF334):​c.-260T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,056 control chromosomes in the GnomAD database, including 22,457 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 0.54 (22455 hom., cov: 32)
  • Exomes 𝑓: 0.75 (2 hom.)
• Consequence: ZNF334 NM_001353824.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70

Genes affected

ZNF334 (HGNC:15806): (zinc finger protein 334) This gene encodes a member of the C2H2 zinc finger family. The encoded protein contains a Krueppel-associated box, fourteen C2H2 zinc finger domains, and four C2H2-type/integrase DNA-binding domains. Decreased expression of this gene may be a marker for rheumatoid arthritis. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF334	NM_001353824.2	c.-260T>G		5_prime_UTR_variant	1/5	ENST00000692313.1	NP_001340753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF334	ENST00000692313.1	c.-260T>G		5_prime_UTR_variant	1/5		NM_001353824.2	ENSP00000510334	P2
ZNF334	ENST00000347606.8	c.-38-621T>G		intron_variant		1		ENSP00000255129	P2
ZNF334	ENST00000457685.6	c.-526T>G		5_prime_UTR_variant	1/6	2		ENSP00000402582
ZNF334	ENST00000625284.2	c.-188-621T>G		intron_variant		2		ENSP00000485779	A2

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81861 AN: 151930 Hom.: 22399 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.531

GnomAD4 exome AF: 0.750 AC: 6 AN: 8 Hom.: 2 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.539 AC: 81973 AN: 152048 Hom.: 22455 Cov.: 32 AF XY: 0.538 AC XY: 40022 AN XY: 74330

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.533

Alfa AF: 0.502 Hom.: 23761

Bravo AF: 0.543

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.58

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: rs366860; hg19: chr20-45141400;