19-53407731-C-A

Variant names:

• chr19-53407731-C-A
• rs566063134
• NM_001040185.3:c.176C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001040185.3(ZNF765):​c.176C>A​(p.Ser59*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,415,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZNF765 NM_001040185.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.11
• Publications: 0 publications found

Genes affected

ZNF765 (HGNC:25092): (zinc finger protein 765) 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]

ZNF765-ZNF761 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040185.3. 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
	ZNF765	NM_001040185.3	MANE Select	c.176C>A	p.Ser59*	stop_gained	Exon 4 of 4	NP_001035275.1	Q7L2R6-1
	ZNF765	NM_001350495.2		c.17C>A	p.Ser6*	stop_gained	Exon 3 of 3	NP_001337424.1
	ZNF765-ZNF761	NM_001350496.2		c.-1345+5540C>A		intron	N/A	NP_001337425.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF765	ENST00000396408.8	TSL:1 MANE Select	c.176C>A	p.Ser59*	stop_gained	Exon 4 of 4	ENSP00000379689.3	Q7L2R6-1
	ZNF765	ENST00000504235.5	TSL:1	n.142+5540C>A		intron	N/A	ENSP00000424395.1	Q7L2R6-2
	ZNF765	ENST00000933978.1		c.176C>A	p.Ser59*	stop_gained	Exon 3 of 3	ENSP00000604037.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1415626 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 700394

African (AFR) AF: 0.00 AC: 0 AN: 31708

American (AMR) AF: 0.00 AC: 0 AN: 36344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23296

East Asian (EAS) AF: 0.00 AC: 0 AN: 39302

South Asian (SAS) AF: 0.00 AC: 0 AN: 77898

European-Finnish (FIN) AF: 0.0000193 AC: 1 AN: 51864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5520

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091368

Other (OTH) AF: 0.00 AC: 0 AN: 58326

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.71
Eigen	Benign	-0.56
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0041	N
PhyloP100		-5.1
Vest4		0.035
GERP RS		-2.0
Mutation Taster		=185/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs566063134; hg19: chr19-53910984;