19-53407952-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040185.3(ZNF765):c.397A>T(p.Asn133Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF765 NM_001040185.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.634

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24800402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF765	NM_001040185.3	c.397A>T	p.Asn133Tyr	missense_variant	4/4	ENST00000396408.8
ZNF765-ZNF761	NM_001350496.2	c.-1345+5761A>T		intron_variant
ZNF765	NM_001350495.2	c.238A>T	p.Asn80Tyr	missense_variant	3/3
ZNF765	NR_146721.2	n.260+5761A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF765	ENST00000396408.8	c.397A>T	p.Asn133Tyr	missense_variant	4/4	1	NM_001040185.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.397A>T (p.N133Y) alteration is located in exon 4 (coding exon 3) of the ZNF765 gene. This alteration results from a A to T substitution at nucleotide position 397, causing the asparagine (N) at amino acid position 133 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	16
Dann	Uncertain	0.98
DEOGEN2	Benign	0.056	T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.20	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M;.
MutationTaster	Benign	1.0	N
PROVEAN	Pathogenic	-7.2	D;D
REVEL	Benign	0.026
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.056	T;D
Polyphen		0.95	P;.
Vest4		0.18
MutPred		0.46		Gain of phosphorylation at N133 (P = 0.0403);.;
MVP		0.25
MPC		0.27
ClinPred		0.91	D
GERP RS		1.0
Varity_R		0.17
gMVP		0.013

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-53911205;