19-53407731-C-G

Variant names:

• chr19-53407731-C-G
• NM_001040185.3:c.176C>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.176C>G​(p.Ser59Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,415,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. S59L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZNF765 NM_001040185.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.11

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=0.1911822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF765	NM_001040185.3	c.176C>G	p.Ser59Trp	missense_variant	Exon 4 of 4	ENST00000396408.8	NP_001035275.1
ZNF765	NM_001350495.2	c.17C>G	p.Ser6Trp	missense_variant	Exon 3 of 3		NP_001337424.1
ZNF765-ZNF761	NM_001350496.2	c.-1345+5540C>G		intron_variant	Intron 3 of 12		NP_001337425.1
ZNF765	NR_146721.2	n.260+5540C>G		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF765	ENST00000396408.8	c.176C>G	p.Ser59Trp	missense_variant	Exon 4 of 4	1	NM_001040185.3	ENSP00000379689.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1415626 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 700394

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.16e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.61
DANN	Benign	0.59
DEOGEN2	Benign	0.055	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.049
Sift	Benign	0.080	T;D
Sift4G	Benign	0.18	T;T
Polyphen		0.99	D;.
Vest4		0.23
MutPred		0.43		Loss of disorder (P = 1e-04);.;
MVP		0.16
MPC		0.32
ClinPred		0.36	T
GERP RS		-2.0
Varity_R		0.061
gMVP		0.019

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-53910984;