5-177049105-A-G

Position:

• chr5-177049105-A-G

Variant summary

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

The NM_012279.4(ZNF346):​c.518-1646A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,728 control chromosomes in the GnomAD database, including 14,227 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 0.43 (14227 hom., cov: 32)
• Consequence: ZNF346 NM_012279.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF346	NM_012279.4	c.518-1646A>G		intron_variant		ENST00000358149.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF346	ENST00000358149.8	c.518-1646A>G		intron_variant		1	NM_012279.4	P1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65157 AN: 151612 Hom.: 14217 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.430 AC: 65198 AN: 151728 Hom.: 14227 Cov.: 32 AF XY: 0.430 AC XY: 31898 AN XY: 74122

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.411

Alfa AF: 0.425 Hom.: 2254

Bravo AF: 0.418

Asia WGS AF: 0.448 AC: 1559 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs251843; hg19: chr5-176476106;