5-177049105-A-G

Variant names:

• chr5-177049105-A-G
• rs251843
• NM_012279.4:c.518-1646A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF346	NM_012279.4	c.518-1646A>G		intron_variant	Intron 4 of 6	ENST00000358149.8	NP_036411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF346	ENST00000358149.8	c.518-1646A>G		intron_variant	Intron 4 of 6	1	NM_012279.4	ENSP00000350869.3

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

African (AFR) AF: 0.408 AC: 16895 AN: 41364

American (AMR) AF: 0.341 AC: 5199 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1403 AN: 3466

East Asian (EAS) AF: 0.473 AC: 2438 AN: 5150

South Asian (SAS) AF: 0.369 AC: 1775 AN: 4812

European-Finnish (FIN) AF: 0.475 AC: 4970 AN: 10460

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.456 AC: 30989 AN: 67932

Other (OTH) AF: 0.411 AC: 864 AN: 2104

Alfa AF: 0.415 Hom.: 3349

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
PhyloP100		0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs251843; hg19: chr5-176476106;