9-66918338-T-A

Position:

• chr9-66918338-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033160.7(ZNF658):​c.772T>A​(p.Phe258Ile) 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. 6/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 27)
• Consequence: ZNF658 NM_033160.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.61

Genes affected

ZNF658 (HGNC:25226): (zinc finger protein 658) Enables transcription cis-regulatory region binding activity. Involved in cellular response to zinc ion; negative regulation of transcription, DNA-templated; and ribosome biogenesis. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064717084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF658	NM_033160.7	c.772T>A	p.Phe258Ile	missense_variant	5/5	ENST00000621410.5	NP_149350.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF658	ENST00000621410.5	c.772T>A	p.Phe258Ile	missense_variant	5/5	2	NM_033160.7	ENSP00000482447	P1
ZNF658	ENST00000622180.4	c.772T>A	p.Phe258Ile	missense_variant, NMD_transcript_variant	5/7	1		ENSP00000480919
ZNF658	ENST00000612867.4	c.772T>A	p.Phe258Ile	missense_variant	5/5	2		ENSP00000482540	P1
ZNF658	ENST00000619925.4	c.772T>A	p.Phe258Ile	missense_variant	5/5	5		ENSP00000479295

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 27

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

Nov 21, 2022

The c.772T>A (p.F258I) alteration is located in exon 5 (coding exon 4) of the ZNF658 gene. This alteration results from a T to A substitution at nucleotide position 772, causing the phenylalanine (F) at amino acid position 258 to be replaced by an isoleucine (I). 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	0.075
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.75
DEOGEN2	Benign	0.0013	.;T;T
LIST_S2	Benign	0.53	T;T;.
MetaRNN	Benign	0.065	T;T;T
Sift4G	Benign	0.58	T;T;T
Vest4		0.30, 0.30
gMVP		0.68

Splicing

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: chr9-40774503;