19-50044819-CTA-GTC

Variant names:

• chr19-50044819-CTA-GTC
• NM_015428.4:c.376_378delCTAinsGTC
• ZNF473 p.Leu126Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015428.4(ZNF473):​c.376_378delCTAinsGTC​(p.Leu126Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF473 NM_015428.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 0 publications found

Genes affected

ZNF473 (HGNC:23239): (zinc finger protein 473) This gene encodes a member of the Krueppel C2H2-type zinc-finger family of proteins. The encoded protein, a component of the U7 snRNP complex, plays a role in histone 3'-end pre-mRNA processing and may be required for cell cycle progression to S phase. Expression level and methylation status of this gene may be correlated with bone mineral density. [provided by RefSeq, Jul 2016]

ZNF473-AS1 (HGNC:58330):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015428.4. 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
	ZNF473	NM_015428.4	MANE Select	c.376_378delCTAinsGTC	p.Leu126Val	missense	N/A	NP_056243.1	Q8WTR7
	ZNF473	NM_001006656.4		c.376_378delCTAinsGTC	p.Leu126Val	missense	N/A	NP_001006657.1	Q8WTR7
	ZNF473	NM_001308424.3		c.340_342delCTAinsGTC	p.Leu114Val	missense	N/A	NP_001295353.1	F8WEC7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF473	ENST00000270617.8	TSL:1 MANE Select	c.376_378delCTAinsGTC	p.Leu126Val	missense	N/A	ENSP00000270617.3	Q8WTR7
	ZNF473	ENST00000391821.6	TSL:1	c.376_378delCTAinsGTC	p.Leu126Val	missense	N/A	ENSP00000375697.1	Q8WTR7
	ZNF473	ENST00000595661.5	TSL:5	c.376_378delCTAinsGTC	p.Leu126Val	missense	N/A	ENSP00000472808.1	Q8WTR7

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
PhyloP100		-0.065

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-50548076;