chr19-57253402-G-A

Position:

• chr19-57253402-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001023563.4(ZNF805):​c.583G>A​(p.Val195Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,560,380 control chromosomes in the GnomAD database, including 193,455 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15754 hom., cov: 33)
  • Exomes 𝑓: 0.50 (177701 hom.)
• Consequence: ZNF805 NM_001023563.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85

Genes affected

ZNF805 (HGNC:23272): (zinc finger protein 805) 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.5325684E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF805	NM_001023563.4	c.583G>A	p.Val195Ile	missense_variant	4/4	ENST00000414468.3	NP_001018857.2
ZNF805	NM_001145078.2	c.184G>A	p.Val62Ile	missense_variant	3/3		NP_001138550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF805	ENST00000414468.3	c.583G>A	p.Val195Ile	missense_variant	4/4	5	NM_001023563.4	ENSP00000412999	P1
ZNF805	ENST00000354309.4	c.184G>A	p.Val62Ile	missense_variant	3/3	5		ENSP00000365414

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66475 AN: 152064 Hom.: 15757 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.452

GnomAD3 exomes AF: 0.467 AC: 78947 AN: 169132 Hom.: 19435 AF XY: 0.474 AC XY: 42670 AN XY: 89988

Gnomad AFR exome AF: 0.277

Gnomad AMR exome AF: 0.424

Gnomad ASJ exome AF: 0.540

Gnomad EAS exome AF: 0.157

Gnomad SAS exome AF: 0.492

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.520

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.497 AC: 699732 AN: 1408200 Hom.: 177701 Cov.: 57 AF XY: 0.499 AC XY: 346994 AN XY: 695624

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.538

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.557

Gnomad4 NFE exome AF: 0.516

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.437 AC: 66471 AN: 152180 Hom.: 15754 Cov.: 33 AF XY: 0.438 AC XY: 32621 AN XY: 74394

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.454

Alfa AF: 0.495 Hom.: 40235

Bravo AF: 0.419

TwinsUK AF: 0.515 AC: 1911

ALSPAC AF: 0.514 AC: 1980

ESP6500AA AF: 0.271 AC: 375

ESP6500EA AF: 0.518 AC: 1647

ExAC AF: 0.387 AC: 43753

Asia WGS AF: 0.322 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0060
DANN	Benign	0.65
DEOGEN2	Benign	0.0018	.;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.0033	T;T
MetaRNN	Benign	0.000035	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.73	.;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.13	N;N
REVEL	Benign	0.0090
Sift	Benign	0.79	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.026	.;B
Vest4		0.024
MPC		0.20
ClinPred		0.012	T
GERP RS		-8.7
Varity_R		0.028
gMVP		0.012

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

LitVar

Other links and lift over

dbSNP: rs10421632; hg19: chr19-57764770; COSMIC: COSV62832324;