chr17-5106218-T-C

Variant names:

• chr17-5106218-T-C
• rs760531158
• NM_014519.6:c.941A>G

Variant summary

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

The NM_014519.6(ZNF232):​c.941A>G​(p.Tyr314Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,614,158 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 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000072 (0 hom.)
• Consequence: ZNF232 NM_014519.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.764
• Publications: 0 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: 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=0.14003134).

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.941A>G	p.Tyr314Cys	missense	Exon 4 of 4	NP_055334.2
	ZNF232	NM_001320952.1		c.914A>G	p.Tyr305Cys	missense	Exon 4 of 4	NP_001307881.1	Q9UNY5-2
	ZNF232	NM_001320953.2		c.860A>G	p.Tyr287Cys	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.941A>G	p.Tyr314Cys	missense	Exon 4 of 4	ENSP00000250076.3	Q9UNY5-1
	ZNF232	ENST00000575898.5	TSL:1	c.914A>G	p.Tyr305Cys	missense	Exon 4 of 4	ENSP00000461305.1	Q9UNY5-2
	ZNF232	ENST00000895122.1		c.1049A>G	p.Tyr350Cys	missense	Exon 4 of 4	ENSP00000565181.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152278 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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251458 AF XY: 0.0000441

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: 0.0000791

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000718 AC: 105 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.0000811 AC XY: 59 AN XY: 727238

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

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

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000899 AC: 100 AN: 1112010

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74404

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68052

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

Alfa AF: 0.000102 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000109

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	0.51
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.76
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.077
Sift	Benign	0.17	T
Sift4G	Benign	0.091	T
Vest4		0.50
MVP		0.040
MPC		0.25
ClinPred		0.26	T
GERP RS		0.60
gMVP		0.092
Mutation Taster		=99/1	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: rs760531158; hg19: chr17-5009513;