19-44264365-C-T

Variant names:

• chr19-44264365-C-T
• rs751891601
• NM_001207005.2:c.5C>T

Variant summary

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

The NM_001207005.2(ZNF233):​c.5C>T​(p.Thr2Ile) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T2N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF233 NM_001207005.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869
• Publications: 0 publications found

Genes affected

ZNF233 (HGNC:30946): (zinc finger protein 233) 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF235 (HGNC:12866): (zinc finger protein 235) This gene product belongs to the zinc finger protein superfamily, members of which are regulatory proteins characterized by nucleic acid-binding zinc finger domains. The encoded protein is a member of the Kruppel family of zinc finger proteins, and contains Kruppel-associated box (KRAB) A and B domains and 15 tandemly arrayed C2H2-type zinc fingers. It is an ortholog of the mouse Zfp93 protein. This gene is located in a cluster of zinc finger genes on 19q13.2. [provided by RefSeq, Jul 2008]

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=0.23337245).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001207005.2. 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
	ZNF233	NM_001207005.2	MANE Select	c.5C>T	p.Thr2Ile	missense	Exon 2 of 5	NP_001193934.1	A6NK53
	ZNF233	NM_181756.3		c.5C>T	p.Thr2Ile	missense	Exon 2 of 5	NP_861421.2	A6NK53
	ZNF233	NM_001330529.2		c.5C>T	p.Thr2Ile	missense	Exon 2 of 5	NP_001317458.1	K7ER86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF233	ENST00000683810.1	MANE Select	c.5C>T	p.Thr2Ile	missense	Exon 2 of 5	ENSP00000507588.1	A6NK53
	ZNF235	ENST00000589799.5	TSL:1	c.239-27636G>A		intron	N/A	ENSP00000468695.1	K7ESF8
	ZNF233	ENST00000391958.6	TSL:2	c.5C>T	p.Thr2Ile	missense	Exon 2 of 5	ENSP00000375820.1	A6NK53

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250496 AF XY: 0.00000738

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: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.2
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.099
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.76	N
PhyloP100		0.87
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.074
Sift	Benign	0.061	T
Sift4G	Benign	0.069	T
Polyphen		1.0	D
Vest4		0.10
MutPred		0.34		Loss of ubiquitination at K3 (P = 0.0583)
MVP		0.27
MPC		0.083
ClinPred		0.38	T
GERP RS		3.0
PromoterAI		0.0056	Neutral
Varity_R		0.067
gMVP		0.042
Mutation Taster		=87/13	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: rs751891601; hg19: chr19-44768518;