19-37388950-C-CTGT

Variant names:

• chr19-37388950-C-CTGT
• rs376931538
• NM_032453.2:c.901_902insTGT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_032453.2(ZNF527):​c.901_902insTGT​(p.Pro301delinsLeuSer) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF527 NM_032453.2 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 10 publications found

Genes affected

ZNF527 (HGNC:29385): (zinc finger protein 527) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_032453.2. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032453.2. 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
	ZNF527	NM_032453.2	MANE Select	c.901_902insTGT	p.Pro301delinsLeuSer	disruptive_inframe_insertion	Exon 5 of 5	NP_115829.1	Q8NB42-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF527	ENST00000436120.7	TSL:4 MANE Select	c.901_902insTGT	p.Pro301delinsLeuSer	disruptive_inframe_insertion	Exon 5 of 5	ENSP00000390179.2	Q8NB42-1
	ZNF527	ENST00000969391.1		c.901_902insTGT	p.Pro301delinsLeuSer	disruptive_inframe_insertion	Exon 5 of 5	ENSP00000639450.1
	ZNF527	ENST00000587349.1	TSL:3	c.*5-3465_*5-3464insTGT		intron	N/A	ENSP00000466096.1	K7ELI5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs376931538; hg19: chr19-37879852;