NM_001040185.3:c.589C>G

Variant names:

• chr19-53408144-C-G
• NM_001040185.3:c.589C>G

Variant summary

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

The NM_001040185.3(ZNF765):​c.589C>G​(p.Leu197Val) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L197Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF765 NM_001040185.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.809

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=0.074141175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF765	NM_001040185.3	c.589C>G	p.Leu197Val	missense_variant	Exon 4 of 4	ENST00000396408.8	NP_001035275.1
ZNF765	NM_001350495.2	c.430C>G	p.Leu144Val	missense_variant	Exon 3 of 3		NP_001337424.1
ZNF765-ZNF761	NM_001350496.2	c.-1345+5953C>G		intron_variant	Intron 3 of 12		NP_001337425.1
ZNF765	NR_146721.2	n.260+5953C>G		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF765	ENST00000396408.8	c.589C>G	p.Leu197Val	missense_variant	Exon 4 of 4	1	NM_001040185.3	ENSP00000379689.3

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

Jun 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.589C>G (p.L197V) alteration is located in exon 4 (coding exon 3) of the ZNF765 gene. This alteration results from a C to G substitution at nucleotide position 589, causing the leucine (L) at amino acid position 197 to be replaced by a valine (V). 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	0.073
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.34
DANN	Benign	0.11
DEOGEN2	Benign	0.0087	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.032	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.0030
Sift	Benign	0.38	T
Sift4G	Benign	0.59	T
Polyphen		0.30	B
Vest4		0.021
MutPred		0.29		Loss of stability (P = 0.0872);
MVP		0.14
MPC		0.062
ClinPred		0.14	T
GERP RS		-1.2
Varity_R		0.085
gMVP		0.0027

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: chr19-53911397;