chr19-43914541-T-C

Position:

• chr19-43914541-T-C

Variant summary

Our verdict is Benign. Variant got -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. 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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=1.0673314E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF45	NM_003425.4	c.895A>G	p.Thr299Ala	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.895A>G	p.Thr299Ala	missense_variant	10/10	2	NM_003425.4	ENSP00000269973.4

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

GnomAD3 exomes AF: 0.537 AC: 134632 AN: 250774 Hom.: 38346 AF XY: 0.526 AC XY: 71241 AN XY: 135522

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 SAS exome AF: 0.403

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

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: 0.401

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.499

Gnomad4 OTH exome AF: 0.507

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

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.487

Alfa AF: 0.507 Hom.: 51260

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 v4.3

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;T;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;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.47	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.5	D;.;.
REVEL	Benign	0.031
Sift	Benign	0.054	T;.;.
Sift4G	Uncertain	0.043	D;D;D
Polyphen		0.0	B;B;B
Vest4		0.0070
MPC		0.18
ClinPred		0.0087	T
GERP RS		-2.2
Varity_R		0.062
gMVP		0.029

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: rs388706; hg19: chr19-44418693; COSMIC: COSV54194149; COSMIC: COSV54194149;