rs388706

Variant names:

• chr19-43914541-T-C
• rs388706
• NM_003425.4:c.895A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003425.4(ZNF45):​c.895A>G​(p.Thr299Ala) 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 1,613,016 control chromosomes in the GnomAD database, including 210,156 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.48 (18709 hom., cov: 32)
  • Exomes 𝑓: 0.51 (191447 hom.)
• Consequence: ZNF45 NM_003425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554
• Publications: 48 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=1.0673314E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 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.895A>G	p.Thr299Ala	missense	Exon 10 of 10	NP_003416.1	Q02386
	ZNF45-AS1	NR_184050.1		n.280-10601T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF45	ENST00000269973.10	TSL:2 MANE Select	c.895A>G	p.Thr299Ala	missense	Exon 10 of 10	ENSP00000269973.4	Q02386
	ZNF45	ENST00000589703.5	TSL:1	c.895A>G	p.Thr299Ala	missense	Exon 4 of 4	ENSP00000468579.1	Q02386
	ZNF45	ENST00000615985.4	TSL:5	c.895A>G	p.Thr299Ala	missense	Exon 5 of 5	ENSP00000481895.1	Q02386

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73496 AN: 151638 Hom.: 18684 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.484

GnomAD2 exomes AF: 0.537 AC: 134632 AN: 250774 AF XY: 0.526

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.707

Gnomad ASJ exome AF: 0.494

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: 739433 AN: 1461258 Hom.: 191447 Cov.: 63 AF XY: 0.502 AC XY: 364809 AN XY: 726892

African (AFR) AF: 0.346 AC: 11578 AN: 33476

American (AMR) AF: 0.696 AC: 31112 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 12780 AN: 26094

East Asian (EAS) AF: 0.833 AC: 33083 AN: 39698

South Asian (SAS) AF: 0.401 AC: 34536 AN: 86148

European-Finnish (FIN) AF: 0.530 AC: 28266 AN: 53374

Middle Eastern (MID) AF: 0.447 AC: 2575 AN: 5764

European-Non Finnish (NFE) AF: 0.499 AC: 554865 AN: 1111638

Other (OTH) AF: 0.507 AC: 30638 AN: 60376

GnomAD4 genome AF: 0.485 AC: 73558 AN: 151758 Hom.: 18709 Cov.: 32 AF XY: 0.490 AC XY: 36328 AN XY: 74152

African (AFR) AF: 0.354 AC: 14663 AN: 41454

American (AMR) AF: 0.627 AC: 9561 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1694 AN: 3470

East Asian (EAS) AF: 0.812 AC: 4173 AN: 5138

South Asian (SAS) AF: 0.420 AC: 2022 AN: 4816

European-Finnish (FIN) AF: 0.515 AC: 5410 AN: 10514

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34340 AN: 67820

Other (OTH) AF: 0.487 AC: 1024 AN: 2102

Alfa AF: 0.503 Hom.: 72565

Bravo AF: 0.491

TwinsUK AF: 0.499 AC: 1851

ALSPAC AF: 0.499 AC: 1923

ESP6500AA AF: 0.358 AC: 1578

ESP6500EA AF: 0.506 AC: 4351

ExAC AF: 0.527 AC: 64005

Asia WGS AF: 0.593 AC: 2059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.98
DANN	Benign	0.33
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.062	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.47	N
PhyloP100		-0.55
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.031
Sift	Benign	0.054	T
Sift4G	Uncertain	0.043	D
Polyphen		0.0	B
Vest4		0.0070
MPC		0.18
ClinPred		0.0087	T
GERP RS		-2.2
Varity_R		0.062
gMVP		0.029
Mutation Taster		=98/2	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: rs388706; hg19: chr19-44418693; COSMIC: COSV54194149; COSMIC: COSV54194149;