19-43913925-C-T

Position:

• chr19-43913925-C-T

Variant summary

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

The NM_003425.4(ZNF45):​c.1511G>A​(p.Arg504Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,612,264 control chromosomes in the GnomAD database, including 210,156 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.49 (18785 hom., cov: 30)
  • Exomes 𝑓: 0.51 (191371 hom.)
• Consequence: ZNF45 NM_003425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

Genes affected

ZNF45 (HGNC:13111): (zinc finger protein 45) 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 nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF45-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.285123E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF45	NM_003425.4	c.1511G>A	p.Arg504Lys	missense_variant	10/10	ENST00000269973.10	NP_003416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF45	ENST00000269973.10	c.1511G>A	p.Arg504Lys	missense_variant	10/10	2	NM_003425.4	ENSP00000269973.4

Frequencies

GnomAD3 genomes AF: 0.488 AC: 73590 AN: 150698 Hom.: 18761 Cov.: 30

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.450

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.485

GnomAD3 exomes AF: 0.538 AC: 134856 AN: 250878 Hom.: 38392 AF XY: 0.526 AC XY: 71379 AN XY: 135574

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.708

Gnomad ASJ exome AF: 0.495

Gnomad EAS exome AF: 0.818

Gnomad SAS exome AF: 0.404

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.510

Gnomad OTH exome AF: 0.526

GnomAD4 exome AF: 0.506 AC: 739506 AN: 1461446 Hom.: 191371 Cov.: 60 AF XY: 0.502 AC XY: 364869 AN XY: 726970

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.696

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.833

Gnomad4 SAS exome AF: 0.402

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.499

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.488 AC: 73650 AN: 150818 Hom.: 18785 Cov.: 30 AF XY: 0.494 AC XY: 36384 AN XY: 73656

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.488

Alfa AF: 0.510 Hom.: 46041

Bravo AF: 0.491

TwinsUK AF: 0.500 AC: 1855

ALSPAC AF: 0.500 AC: 1926

ESP6500AA AF: 0.359 AC: 1581

ESP6500EA AF: 0.506 AC: 4351

ExAC AF: 0.527 AC: 64003

Asia WGS AF: 0.593 AC: 2060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.88
DEOGEN2	Benign	0.010	T;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.00047	N
LIST_S2	Benign	0.0087	.;T;.
MetaRNN	Benign	7.3e-7	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.21	N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	1.1	N;.;.
REVEL	Benign	0.034
Sift	Benign	0.32	T;.;.
Sift4G	Benign	0.56	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.026
MPC		0.18
ClinPred		0.0069	T
GERP RS		2.6
Varity_R		0.089
gMVP		0.023

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: rs407731; hg19: chr19-44418077;