19-53407838-C-A

Variant names:

• chr19-53407838-C-A
• rs746730483
• NM_001040185.3:c.283C>A

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.283C>A​(p.His95Asn) 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. 13/21 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: -1.95
• Publications: 1 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=0.11141205).

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.283C>A	p.His95Asn	missense	Exon 4 of 4	NP_001035275.1	Q7L2R6-1
	ZNF765	NM_001350495.2		c.124C>A	p.His42Asn	missense	Exon 3 of 3	NP_001337424.1
	ZNF765-ZNF761	NM_001350496.2		c.-1345+5647C>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.283C>A	p.His95Asn	missense	Exon 4 of 4	ENSP00000379689.3	Q7L2R6-1
	ZNF765	ENST00000504235.5	TSL:1	n.142+5647C>A		intron	N/A	ENSP00000424395.1	Q7L2R6-2
	ZNF765	ENST00000933978.1		c.283C>A	p.His95Asn	missense	Exon 3 of 3	ENSP00000604037.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249602 AF XY: 0.00000739

Gnomad AFR exome AF: 0.0000638

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.6
DANN	Benign	0.71
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		-2.0
PROVEAN	Pathogenic	-6.1	D
REVEL	Benign	0.084
Sift	Benign	0.063	T
Sift4G	Benign	0.12	T
Polyphen		0.092	B
Vest4		0.12
MutPred		0.22		Loss of ubiquitination at K92 (P = 0.1498)
MVP		0.13
MPC		0.051
ClinPred		0.20	T
GERP RS		0.072
Varity_R		0.14
gMVP		0.013
Mutation Taster		=100/0	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: rs746730483; hg19: chr19-53911091;