19-53407845-T-C

Variant summary

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

The NM_001040185.3(ZNF765):c.290T>C(p.Ile97Thr) 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. 13/20 in silico tools predict 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: -1.66

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=0.0717673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF765	NM_001040185.3	c.290T>C	p.Ile97Thr	missense_variant	4/4	ENST00000396408.8
ZNF765-ZNF761	NM_001350496.2	c.-1345+5654T>C		intron_variant
ZNF765	NM_001350495.2	c.131T>C	p.Ile44Thr	missense_variant	3/3
ZNF765	NR_146721.2	n.260+5654T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF765	ENST00000396408.8	c.290T>C	p.Ile97Thr	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

Jan 03, 2024

The c.290T>C (p.I97T) alteration is located in exon 4 (coding exon 3) of the ZNF765 gene. This alteration results from a T to C substitution at nucleotide position 290, causing the isoleucine (I) at amino acid position 97 to be replaced by a threonine (T). 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	0.092
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	8.1
Dann	Benign	0.71
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.011	N
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.90	L;.
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-2.3	N;D
REVEL	Benign	0.025
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.086	T;D
Polyphen		0.025	B;.
Vest4		0.040
MutPred		0.41		Gain of disorder (P = 0.0211);.;
MVP		0.040
MPC		0.062
ClinPred		0.094	T
GERP RS		0.65
Varity_R		0.085
gMVP		0.0089

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: chr19-53911098;