5-177076562-A-G

Position:

• chr5-177076562-A-G

Variant summary

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

The NM_001308213.2(ZNF346):​c.*3-2820A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,842 control chromosomes in the GnomAD database, including 26,357 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 0.59 (26357 hom., cov: 31)
• Consequence: ZNF346 NM_001308213.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61

Genes affected

ZNF346 (HGNC:16403): (zinc finger protein 346) The protein encoded by this gene is a nucleolar, zinc finger protein that preferentially binds to double-stranded (ds) RNA or RNA/DNA hybrids, rather than DNA alone. Mutational studies indicate that the zinc finger domains are not only essential for dsRNA binding, but are also required for its nucleolar localization. The encoded protein may be involved in cell growth and survival. It plays a role in protecting neurons by inhibiting cell cycle re-entry via stimulation of p21 gene expression. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

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 (AMR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF346	NM_001308213.2	c.*3-2820A>G		intron_variant
ZNF346	NM_001308219.2	c.463-2820A>G		intron_variant
ZNF346	NM_001308223.2	c.*3-2820A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF346	ENST00000503039.1	c.*3-2820A>G		intron_variant		2
ZNF346	ENST00000512315.5	c.*3-2820A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88773 AN: 151720 Hom.: 26320 Cov.: 31

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.603

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.585 AC: 88864 AN: 151842 Hom.: 26357 Cov.: 31 AF XY: 0.584 AC XY: 43290 AN XY: 74174

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.600

Alfa AF: 0.554 Hom.: 6356

Bravo AF: 0.598

Asia WGS AF: 0.573 AC: 1992 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	0.63
DANN	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs244715; hg19: chr5-176503563; COSMIC: COSV72296516;