chr17-5106102-G-A

Variant names:

• chr17-5106102-G-A
• rs1309754378
• NM_014519.6:c.1057C>T

Variant summary

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

The NM_014519.6(ZNF232):​c.1057C>T​(p.His353Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. H353D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF232 NM_014519.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.34
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1057C>T	p.His353Tyr	missense	Exon 4 of 4	NP_055334.2
	ZNF232	NM_001320952.1		c.1030C>T	p.His344Tyr	missense	Exon 4 of 4	NP_001307881.1	Q9UNY5-2
	ZNF232	NM_001320953.2		c.976C>T	p.His326Tyr	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.1057C>T	p.His353Tyr	missense	Exon 4 of 4	ENSP00000250076.3	Q9UNY5-1
	ZNF232	ENST00000575898.5	TSL:1	c.1030C>T	p.His344Tyr	missense	Exon 4 of 4	ENSP00000461305.1	Q9UNY5-2
	ZNF232	ENST00000895122.1		c.1165C>T	p.His389Tyr	missense	Exon 4 of 4	ENSP00000565181.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.80
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.26	D
PhyloP100		8.3
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Vest4		0.48
MVP		0.71
MPC		0.070
ClinPred		0.98	D
GERP RS		2.8
gMVP		0.070

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: rs1309754378; hg19: chr17-5009397;