9-66908259-G-C

Position:

• chr9-66908259-G-C

Variant summary

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

The NM_033160.7(ZNF658):​c.37G>C​(p.Val13Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V13M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ZNF658 NM_033160.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63

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 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=0.1352537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF658	NM_033160.7	c.37G>C	p.Val13Leu	missense_variant	3/5	ENST00000621410.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF658	ENST00000621410.5	c.37G>C	p.Val13Leu	missense_variant	3/5	2	NM_033160.7	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

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

Mar 06, 2023

The c.37G>C (p.V13L) alteration is located in exon 3 (coding exon 2) of the ZNF658 gene. This alteration results from a G to C substitution at nucleotide position 37, causing the valine (V) at amino acid position 13 to be replaced by a leucine (L). 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	Pathogenic	0.60
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Uncertain	0.99
LIST_S2	Benign	0.84	T;T;T;.;T
MetaRNN	Benign	0.14	T;T;T;T;T
Sift4G	Benign	0.071	T;D;D;D;D
Vest4		0.52, 0.52
gMVP		0.76

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: chr9-40784582;