5-177076562-A-G

Variant names:

• chr5-177076562-A-G
• rs244715
• NM_001308213.2:c.*3-2820A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308213.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF346	NM_001308213.2		c.*3-2820A>G		intron	N/A	NP_001295142.1	Q9UL40-2
	ZNF346	NM_001363713.2		c.*3-2820A>G		intron	N/A	NP_001350642.1	D6RJ07
	ZNF346	NM_001308219.2		c.463-2820A>G		intron	N/A	NP_001295148.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF346	ENST00000503039.1	TSL:2	c.*3-2820A>G		intron	N/A	ENSP00000424495.1	Q9UL40-2
	ZNF346	ENST00000883439.1		c.*3-2820A>G		intron	N/A	ENSP00000553498.1
	ZNF346	ENST00000883438.1		c.*3-2820A>G		intron	N/A	ENSP00000553497.1

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

African (AFR) AF: 0.648 AC: 26815 AN: 41408

American (AMR) AF: 0.664 AC: 10118 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2055 AN: 3472

East Asian (EAS) AF: 0.546 AC: 2815 AN: 5160

South Asian (SAS) AF: 0.634 AC: 3044 AN: 4798

European-Finnish (FIN) AF: 0.521 AC: 5483 AN: 10528

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36740 AN: 67934

Other (OTH) AF: 0.600 AC: 1262 AN: 2102

Alfa AF: 0.559 Hom.: 8315

Bravo AF: 0.598

Asia WGS AF: 0.573 AC: 1992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.27
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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