chr19-44097881-C-T

Variant names:

• chr19-44097881-C-T
• rs552259920
• NM_001321645.3:c.8C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001321645.3(ZNF224):​c.8C>T​(p.Thr3Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: ZNF224 NM_001321645.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.67
• Publications: 2 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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019549698).
• BP6: Variant 19-44097881-C-T is Benign according to our data. Variant chr19-44097881-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3820018.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321645.3. 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
	ZNF224	NM_001321645.3	MANE Select	c.8C>T	p.Thr3Met	missense	Exon 3 of 6	NP_001308574.1	Q9NZL3
	ZNF224	NM_013398.5		c.8C>T	p.Thr3Met	missense	Exon 3 of 6	NP_037530.2	Q9NZL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF224	ENST00000693561.1	MANE Select	c.8C>T	p.Thr3Met	missense	Exon 3 of 6	ENSP00000508532.1	Q9NZL3
	ZNF224	ENST00000336976.10	TSL:1	c.8C>T	p.Thr3Met	missense	Exon 3 of 6	ENSP00000337368.5	Q9NZL3
	ZNF224	ENST00000950453.1		c.8C>T	p.Thr3Met	missense	Exon 3 of 6	ENSP00000620512.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250896 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000315 AC: 46 AN: 1461630 Hom.: 0 Cov.: 30 AF XY: 0.0000440 AC XY: 32 AN XY: 727096

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111902

Other (OTH) AF: 0.0000497 AC: 3 AN: 60384

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.069
DANN	Benign	0.27
DEOGEN2	Benign	0.0087	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.00075	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.00094	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.20	N
PhyloP100		-3.7
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.026
Sift	Benign	0.26	T
Sift4G	Benign	0.19	T
Polyphen		0.40	B
Vest4		0.11
MutPred		0.20		Loss of glycosylation at T3 (P = 0.036)
MVP		0.048
MPC		0.10
ClinPred		0.030	T
GERP RS		-4.4
PromoterAI		0.0036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.014
gMVP		0.043
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs552259920; hg19: chr19-44602034; COSMIC: COSV61241722; COSMIC: COSV61241722;