19-53407973-C-T

Variant names:

• chr19-53407973-C-T
• rs766839591
• NM_001040185.3:c.418C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040185.3(ZNF765):​c.418C>T​(p.Leu140Phe) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L140V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF765 NM_001040185.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14163545).

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.418C>T	p.Leu140Phe	missense	Exon 4 of 4	NP_001035275.1	Q7L2R6-1
	ZNF765	NM_001350495.2		c.259C>T	p.Leu87Phe	missense	Exon 3 of 3	NP_001337424.1
	ZNF765-ZNF761	NM_001350496.2		c.-1345+5782C>T		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.418C>T	p.Leu140Phe	missense	Exon 4 of 4	ENSP00000379689.3	Q7L2R6-1
	ZNF765	ENST00000504235.5	TSL:1	n.142+5782C>T		intron	N/A	ENSP00000424395.1	Q7L2R6-2
	ZNF765	ENST00000933978.1		c.418C>T	p.Leu140Phe	missense	Exon 3 of 3	ENSP00000604037.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.074	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		-0.19
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.022
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.055	T
Polyphen		0.62	P
Vest4		0.12
MutPred		0.53		Gain of catalytic residue at L140 (P = 0.0819)
MVP		0.067
MPC		0.32
ClinPred		0.78	D
GERP RS		-1.0
Varity_R		0.13
gMVP		0.0054
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs766839591; hg19: chr19-53911226;