rs251843

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-177049105-A-C
• chr5-177049105-A-G
• chr5-177049105-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012279.4(ZNF346):​c.518-1646A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012279.4. 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_012279.4	MANE Select	c.518-1646A>C		intron	N/A	NP_036411.1	Q9UL40-1
	ZNF346	NM_001308213.2		c.593-1646A>C		intron	N/A	NP_001295142.1	Q9UL40-2
	ZNF346	NM_001363713.2		c.518-1598A>C		intron	N/A	NP_001350642.1	D6RJ07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF346	ENST00000358149.8	TSL:1 MANE Select	c.518-1646A>C		intron	N/A	ENSP00000350869.3	Q9UL40-1
	ZNF346	ENST00000503039.1	TSL:2	c.593-1646A>C		intron	N/A	ENSP00000424495.1	Q9UL40-2
	ZNF346	ENST00000883448.1		c.593-1646A>C		intron	N/A	ENSP00000553507.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.57
PhyloP100		0.45

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;