19-43913925-C-T

Variant names:

• chr19-43913925-C-T
• rs407731
• NM_003425.4:c.1511G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 0.49 (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
• Publications: 46 publications found

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:55308): (ZNF45 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003425.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF45	NM_003425.4	MANE Select	c.1511G>A	p.Arg504Lys	missense	Exon 10 of 10	NP_003416.1	Q02386
	ZNF45-AS1	NR_184050.1		n.280-11217C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF45	ENST00000269973.10	TSL:2 MANE Select	c.1511G>A	p.Arg504Lys	missense	Exon 10 of 10	ENSP00000269973.4	Q02386
	ZNF45	ENST00000589703.5	TSL:1	c.1511G>A	p.Arg504Lys	missense	Exon 4 of 4	ENSP00000468579.1	Q02386
	ZNF45	ENST00000615985.4	TSL:5	c.1511G>A	p.Arg504Lys	missense	Exon 5 of 5	ENSP00000481895.1	Q02386

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

GnomAD2 exomes AF: 0.538 AC: 134856 AN: 250878 AF XY: 0.526

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 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

African (AFR) AF: 0.346 AC: 11579 AN: 33468

American (AMR) AF: 0.696 AC: 31128 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 12791 AN: 26120

East Asian (EAS) AF: 0.833 AC: 33077 AN: 39686

South Asian (SAS) AF: 0.402 AC: 34639 AN: 86234

European-Finnish (FIN) AF: 0.530 AC: 28286 AN: 53406

Middle Eastern (MID) AF: 0.446 AC: 2574 AN: 5768

European-Non Finnish (NFE) AF: 0.499 AC: 554783 AN: 1111680

Other (OTH) AF: 0.508 AC: 30649 AN: 60372

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

African (AFR) AF: 0.358 AC: 14640 AN: 40940

American (AMR) AF: 0.629 AC: 9581 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1684 AN: 3444

East Asian (EAS) AF: 0.814 AC: 4165 AN: 5114

South Asian (SAS) AF: 0.426 AC: 2017 AN: 4734

European-Finnish (FIN) AF: 0.521 AC: 5438 AN: 10440

Middle Eastern (MID) AF: 0.446 AC: 125 AN: 280

European-Non Finnish (NFE) AF: 0.509 AC: 34429 AN: 67636

Other (OTH) AF: 0.488 AC: 1025 AN: 2100

Alfa AF: 0.505 Hom.: 66356

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 v4.9

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
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
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.21	N
PhyloP100		1.4
PrimateAI	Benign	0.48	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.034
Sift	Benign	0.32	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.026
MPC		0.18
ClinPred		0.0069	T
GERP RS		2.6
Varity_R		0.089
gMVP		0.023
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs407731; hg19: chr19-44418077; COSMIC: COSV107207442; COSMIC: COSV107207442;