19-43913925-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003425.4(ZNF45):​c.1511G>T​(p.Arg504Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 30)
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07285985).

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>T	p.Arg504Met	missense	Exon 10 of 10	NP_003416.1	Q02386
	ZNF45-AS1	NR_184050.1		n.280-11217C>A		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>T	p.Arg504Met	missense	Exon 10 of 10	ENSP00000269973.4	Q02386
	ZNF45	ENST00000589703.5	TSL:1	c.1511G>T	p.Arg504Met	missense	Exon 4 of 4	ENSP00000468579.1	Q02386
	ZNF45	ENST00000615985.4	TSL:5	c.1511G>T	p.Arg504Met	missense	Exon 5 of 5	ENSP00000481895.1	Q02386

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.056	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.88	L
PhyloP100		1.4
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.040
Sift	Benign	0.080	T
Sift4G	Uncertain	0.049	D
Polyphen		0.060	B
Vest4		0.24
MutPred		0.39		Loss of MoRF binding (P = 0.0601)
MVP		0.21
MPC		0.29
ClinPred		0.30	T
GERP RS		2.6
Varity_R		0.069
gMVP		0.045
Mutation Taster		=96/4	polymorphism

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;