chr19-44106822-C-T

Variant names:

• chr19-44106822-C-T
• rs201293616
• NM_001321645.3:c.662C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001321645.3(ZNF224):​c.662C>T​(p.Thr221Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: ZNF224 NM_001321645.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -8.70
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.01324904).

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.662C>T	p.Thr221Ile	missense	Exon 6 of 6	NP_001308574.1	Q9NZL3
	ZNF224	NM_013398.5		c.662C>T	p.Thr221Ile	missense	Exon 6 of 6	NP_037530.2	Q9NZL3
	ZNF225-AS1	NR_033341.1		n.1878G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF224	ENST00000693561.1	MANE Select	c.662C>T	p.Thr221Ile	missense	Exon 6 of 6	ENSP00000508532.1	Q9NZL3
	ZNF224	ENST00000336976.10	TSL:1	c.662C>T	p.Thr221Ile	missense	Exon 6 of 6	ENSP00000337368.5	Q9NZL3
	ZNF225-AS1	ENST00000592946.1	TSL:1	n.1840G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152150 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000175 AC: 44 AN: 251022 AF XY: 0.000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00378

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000103 AC: 150 AN: 1461522 Hom.: 0 Cov.: 88 AF XY: 0.0000922 AC XY: 67 AN XY: 727056

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00418 AC: 109 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111796

Other (OTH) AF: 0.000298 AC: 18 AN: 60388

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152150 Hom.: 0 Cov.: 34 AF XY: 0.000135 AC XY: 10 AN XY: 74332

African (AFR) AF: 0.0000241 AC: 1 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000428 Hom.: 0

Bravo AF: 0.000147

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.19
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.7
DANN	Benign	0.82
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.68	N
PhyloP100		-8.7
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.014
Sift	Benign	0.27	T
Sift4G	Benign	0.32	T
Polyphen		0.071	B
Vest4		0.051
MVP		0.072
MPC		0.16
ClinPred		0.041	T
GERP RS		-0.20
Varity_R		0.031
gMVP		0.012
Mutation Taster		=98/2	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: rs201293616; hg19: chr19-44610975;