19-57477299-G-GGCC

Variant names:

• chr19-57477299-G-GGCC
• rs193920834
• NM_001144068.2:c.10_11insGGC

Variant summary

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

The NM_001144068.2(ZNF772):​c.10_11insGGC​(p.Ala4delinsGlyPro) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF772 NM_001144068.2 conservative_inframe_insertion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.39
• Publications: 0 publications found

Genes affected

ZNF772 (HGNC:33106): (zinc finger protein 772) 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]

ENSG00000268163 (HGNC:):

PKMYT1AR (HGNC:56847):

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_001144068.2. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144068.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF772	NM_001144068.2	MANE Select	c.10_11insGGC	p.Ala4delinsGlyPro	conservative_inframe_insertion	Exon 1 of 4	NP_001137540.1
	ZNF772	NM_001024596.3		c.10_11insGGC	p.Ala4delinsGlyPro	conservative_inframe_insertion	Exon 1 of 5	NP_001019767.1
	ZNF772	NM_001439216.1		c.10_11insGGC	p.Ala4delinsGlyPro	conservative_inframe_insertion	Exon 1 of 3	NP_001426145.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF772	ENST00000356584.8	TSL:2 MANE Select	c.10_11insGGC	p.Ala4delinsGlyPro	conservative_inframe_insertion	Exon 1 of 4	ENSP00000348992.3
	ZNF772	ENST00000343280.8	TSL:1	c.10_11insGGC	p.Ala4delinsGlyPro	conservative_inframe_insertion	Exon 1 of 5	ENSP00000341165.4
	ENSG00000268163	ENST00000596831.1	TSL:2	c.10_11insGGC	p.Ala4delinsGlyPro	conservative_inframe_insertion	Exon 1 of 6	ENSP00000470969.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs193920834; hg19: chr19-57988667; COSMIC: COSV108172037; COSMIC: COSV108172037;