2-27378154-GCA-CCT

Variant names:

• chr2-27378154-GCA-CCT
• NM_144631.6:c.1015_1017delTGCinsAGG
• ZNF513 p.Cys339Arg

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PS1_Moderate

The NM_144631.6(ZNF513):​c.1015_1017delTGCinsAGG​(p.Cys339Arg) 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 Likely pathogenic in ClinVar. Synonymous variant affecting the same amino acid position (i.e. C339C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF513 NM_144631.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35
• Publications: 0 publications found

Genes affected

ZNF513 (HGNC:26498): (zinc finger protein 513) The protein encoded by this gene is a possible transcriptional regulator involved in retinal development. Defects in this gene can be a cause of autosomal-recessive retinitis pigmentosa. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

ZNF513 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa 58

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PS1: Transcript NM_144631.6 (ZNF513) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144631.6. 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
	ZNF513	NM_144631.6	MANE Select	c.1015_1017delTGCinsAGG	p.Cys339Arg	missense	N/A	NP_653232.3
	ZNF513	NM_001201459.2		c.829_831delTGCinsAGG	p.Cys277Arg	missense	N/A	NP_001188388.1	Q8N8E2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF513	ENST00000323703.11	TSL:1 MANE Select	c.1015_1017delTGCinsAGG	p.Cys339Arg	missense	N/A	ENSP00000318373.6	Q8N8E2-1
	ZNF513	ENST00000407879.1	TSL:1	c.829_831delTGCinsAGG	p.Cys277Arg	missense	N/A	ENSP00000384874.1	Q8N8E2-2
	ZNF513	ENST00000917778.1		c.997_999delTGCinsAGG	p.Cys333Arg	missense	N/A	ENSP00000587837.1

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
PhyloP100		3.4

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: chr2-27601021;