17-5106269-G-A

Variant names:

• chr17-5106269-G-A
• rs201827182
• NM_014519.6:c.890C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014519.6(ZNF232):​c.890C>T​(p.Pro297Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000107 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: ZNF232 NM_014519.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26
• Publications: 3 publications found

Genes affected

ZNF232 (HGNC:13026): (zinc finger protein 232) 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 cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF232-AS1 (HGNC:40623): (ZNF232 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12681696).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014519.6. 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
	ZNF232	NM_014519.6	MANE Select	c.890C>T	p.Pro297Leu	missense	Exon 4 of 4	NP_055334.2
	ZNF232	NM_001320952.1		c.863C>T	p.Pro288Leu	missense	Exon 4 of 4	NP_001307881.1	Q9UNY5-2
	ZNF232	NM_001320953.2		c.809C>T	p.Pro270Leu	missense	Exon 6 of 6	NP_001307882.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF232	ENST00000250076.8	TSL:5 MANE Select	c.890C>T	p.Pro297Leu	missense	Exon 4 of 4	ENSP00000250076.3	Q9UNY5-1
	ZNF232	ENST00000575898.5	TSL:1	c.863C>T	p.Pro288Leu	missense	Exon 4 of 4	ENSP00000461305.1	Q9UNY5-2
	ZNF232	ENST00000895122.1		c.998C>T	p.Pro333Leu	missense	Exon 4 of 4	ENSP00000565181.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152204 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251474 AF XY: 0.0000515

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000615

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000113 AC: 165 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.000118 AC XY: 86 AN XY: 727240

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000139 AC: 155 AN: 1112012

Other (OTH) AF: 0.0000662 AC: 4 AN: 60396

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000172 Hom.: 0

Bravo AF: 0.0000567

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.000119

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	Uncertain	0.39
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
PhyloP100		4.3
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.14
Sift	Benign	0.66	T
Sift4G	Benign	0.70	T
Vest4		0.30
MVP		0.085
MPC		0.037
ClinPred		0.22	T
GERP RS		0.92
gMVP		0.071
Mutation Taster		=92/8	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: rs201827182; hg19: chr17-5009564;