19-22314024-A-G

Position:

• chr19-22314024-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001242680.2(ZNF729):​c.607A>G​(p.Ile203Val) 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF729 NM_001242680.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.279

Genes affected

ZNF729 (HGNC:32464): (zinc finger protein 729) Predicted to enable DNA-binding transcription activator 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08681664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF729	NM_001242680.2	c.607A>G	p.Ile203Val	missense_variant	4/4	ENST00000601693.2	NP_001229609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF729	ENST00000601693.2	c.607A>G	p.Ile203Val	missense_variant	4/4	2	NM_001242680.2	ENSP00000469582.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 14, 2022

The c.607A>G (p.I203V) alteration is located in exon 4 (coding exon 4) of the ZNF729 gene. This alteration results from a A to G substitution at nucleotide position 607, causing the isoleucine (I) at amino acid position 203 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.5
DANN	Benign	0.79
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.28	T
Sift4G	Uncertain	0.017	D
Vest4		0.077
MutPred		0.47		Gain of methylation at K202 (P = 0.0662);
MVP		0.19
MPC		0.010
ClinPred		0.042	T
GERP RS		-0.055
Varity_R		0.021
gMVP		0.0012

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-22496826;