rs193921003

Variant names:

• chr19-44107514-G-A
• rs193921003
• NM_001321645.3:c.1354G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001321645.3(ZNF224):​c.1354G>A​(p.Gly452Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF224 NM_001321645.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.03
• Publications: 1 publications found

Genes affected

ZNF224 (HGNC:13017): (zinc finger protein 224) This gene encodes a member of the Krueppel C2H2-type zinc-finger family of proteins. The encoded protein represses transcription of the aldolase A gene, which encodes a key enzyme in glycolysis. The encoded zinc-finger protein may also function as a transcriptional co-activator with Wilms' tumor protein 1 to regulate apoptotic genes in leukemia. [provided by RefSeq, Jul 2016]

ZNF225-AS1 (HGNC:55916): (ZNF225 and ZNF224 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42072213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF224	NM_001321645.3	c.1354G>A	p.Gly452Arg	missense_variant	Exon 6 of 6	ENST00000693561.1	NP_001308574.1
ZNF224	NM_013398.5	c.1354G>A	p.Gly452Arg	missense_variant	Exon 6 of 6		NP_037530.2
ZNF225-AS1	NR_033341.1	n.1186C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF224	ENST00000693561.1	c.1354G>A	p.Gly452Arg	missense_variant	Exon 6 of 6		NM_001321645.3	ENSP00000508532.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 81

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

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Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.51		Gain of solvent accessibility (P = 0.0037);
MVP		0.43
MPC		0.52
ClinPred		0.99	D
GERP RS		2.9
Varity_R		0.10
gMVP		0.017
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: rs193921003; hg19: chr19-44611667;