19-53455369-C-T

Position:

• chr19-53455369-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001289951.2(ZNF761):​c.862C>T​(p.His288Tyr) 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. 7/11 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: ZNF761 NM_001289951.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.819

Genes affected

ZNF761 (HGNC:23179): (zinc finger protein 761) 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3164848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF761	NM_001289951.2	c.862C>T	p.His288Tyr	missense_variant	5/5	ENST00000684525.1	NP_001276880.1
ZNF765-ZNF761	NM_001350496.2	c.862C>T	p.His288Tyr	missense_variant	13/13		NP_001337425.1
ZNF761	NM_001008401.4	c.862C>T	p.His288Tyr	missense_variant	6/6		NP_001008401.3
ZNF761	NM_001289952.1	c.862C>T	p.His288Tyr	missense_variant	5/5		NP_001276881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF761	ENST00000684525.1	c.862C>T	p.His288Tyr	missense_variant	5/5		NM_001289951.2	ENSP00000507666	P1
	ENST00000657048.1	n.86+18482G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 104

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

May 20, 2024

The c.862C>T (p.H288Y) alteration is located in exon 6 (coding exon 3) of the ZNF761 gene. This alteration results from a C to T substitution at nucleotide position 862, causing the histidine (H) at amino acid position 288 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	Pathogenic	0.63
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.37
DEOGEN2	Benign	0.14	T;T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	.;T
MetaRNN	Benign	0.32	T;T
PrimateAI	Uncertain	0.58	T
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.25
MVP		0.20
GERP RS		0.99
Varity_R		0.065

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: chr19-53958623;