rs34863160

chr19-56578467-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001001668.4(ZNF470):c.2038A>G(p.Lys680Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,612,548 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.011 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (27 hom.)
• Consequence: ZNF470 NM_001001668.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

Genes affected

ZNF470 (HGNC:22220): (zinc finger protein 470) 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. Located in nuclear body. [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=0.0017959774).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1668/152278) while in subpopulation AFR AF= 0.0381 (1583/41562). AF 95% confidence interval is 0.0365. There are 26 homozygotes in gnomad4. There are 771 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF470	NM_001001668.4	c.2038A>G	p.Lys680Glu	missense_variant	6/6	ENST00000330619.13
ZNF470	XM_047438804.1	c.2038A>G	p.Lys680Glu	missense_variant	7/7
ZNF470	XM_047438805.1	c.1885A>G	p.Lys629Glu	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF470	ENST00000330619.13	c.2038A>G	p.Lys680Glu	missense_variant	6/6	1	NM_001001668.4	P1

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1665 AN: 152160 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00296 AC: 738 AN: 249120 Hom.: 10 AF XY: 0.00215 AC XY: 290 AN XY: 134750

Gnomad AFR exome AF: 0.0383

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00315

GnomAD4 exome AF: 0.00124 AC: 1806 AN: 1460270 Hom.: 27 Cov.: 33 AF XY: 0.00106 AC XY: 771 AN XY: 726488

Gnomad4 AFR exome AF: 0.0416

Gnomad4 AMR exome AF: 0.00263

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000131

Gnomad4 OTH exome AF: 0.00222

GnomAD4 genome AF: 0.0110 AC: 1668 AN: 152278 Hom.: 26 Cov.: 32 AF XY: 0.0104 AC XY: 771 AN XY: 74462

Gnomad4 AFR AF: 0.0381

Gnomad4 AMR AF: 0.00418

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00211 Hom.: 11

Bravo AF: 0.0124

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0379 AC: 167

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00359 AC: 436

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	17
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0052	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.043	N
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.33	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.010
Sift	Benign	0.17	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.0010	B;B
Vest4		0.13
MVP		0.16
MPC		0.014
ClinPred		0.0031	T
GERP RS		1.9
Varity_R		0.10
gMVP		0.018

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: rs34863160; hg19: chr19-57089835;