19-7519289-G-A

Position:

• chr19-7519289-G-A

Variant summary

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

The NM_018083.5(ZNF358):​c.47G>A​(p.Arg16Lys) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF358 NM_018083.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.820

Genes affected

ZNF358 (HGNC:16838): (zinc finger protein 358) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in several processes, including embryonic forelimb morphogenesis; neural tube development; and stem cell population maintenance. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267952 (HGNC:):

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=0.0926719).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF358	NM_018083.5	c.47G>A	p.Arg16Lys	missense_variant	2/2	ENST00000597229.2	NP_060553.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF358	ENST00000597229.2	c.47G>A	p.Arg16Lys	missense_variant	2/2	2	NM_018083.5	ENSP00000472305.1
ENSG00000267952	ENST00000599312.1	c.*1G>A		3_prime_UTR_variant	2/2	2		ENSP00000469588.1
ZNF358	ENST00000596712.1	c.47G>A	p.Arg16Lys	missense_variant	2/2	3		ENSP00000472777.1
ENSG00000267952	ENST00000597384.1	n.301G>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

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

Dec 14, 2023

The c.47G>A (p.R16K) alteration is located in exon 2 (coding exon 1) of the ZNF358 gene. This alteration results from a G to A substitution at nucleotide position 47, causing the arginine (R) at amino acid position 16 to be replaced by a lysine (K). 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	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.00051	.;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Uncertain	0.53	T
Sift4G	Benign	0.31	T;T
Polyphen		0.010	.;B
Vest4		0.068
MutPred		0.28		Gain of ubiquitination at R16 (P = 0.0101);Gain of ubiquitination at R16 (P = 0.0101);
MVP		0.48
ClinPred		0.13	T
GERP RS		2.4
Varity_R		0.047
gMVP		0.11

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: chr19-7584175;