Variant 5-177022908-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012279.4(ZNF346):c.170A>G(p.Glu57Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000302 in 1,325,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

ZNF346
NM_012279.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

Variant links:

Genes affected

ZNF346 (HGNC:16403): (zinc finger protein 346) The protein encoded by this gene is a nucleolar, zinc finger protein that preferentially binds to double-stranded (ds) RNA or RNA/DNA hybrids, rather than DNA alone. Mutational studies indicate that the zinc finger domains are not only essential for dsRNA binding, but are also required for its nucleolar localization. The encoded protein may be involved in cell growth and survival. It plays a role in protecting neurons by inhibiting cell cycle re-entry via stimulation of p21 gene expression. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ZNF346 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27136478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF346	NM_012279.4 linkuse as main transcript	c.170A>G	p.Glu57Gly	missense_variant	1/7	ENST00000358149.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF346	ENST00000358149.8 linkuse as main transcript	c.170A>G	p.Glu57Gly	missense_variant	1/7	1	NM_012279.4	P1	Q9UL40-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000302

AC:

AN:

1325964

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

647588

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000583

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.170A>G (p.E57G) alteration is located in exon 1 (coding exon 1) of the ZNF346 gene. This alteration results from a A to G substitution at nucleotide position 170, causing the glutamic acid (E) at amino acid position 57 to be replaced by a glycine (G). 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

0.19

BayesDel_addAF

Benign

0.0058

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;T;.;.;T;.

Eigen

Benign

0.075

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.91

D;D;T;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.27

T;T;T;T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.90

.;L;.;L;.;L

MutationTaster

Benign

0.92

D;D;D;N;N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.7

N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0070

D;T;T;T;T;D

Sift4G

Uncertain

0.050

T;T;T;T;T;T

Polyphen

0.99

D;P;D;.;.;B

Vest4

0.49

MutPred

0.43

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);

MVP

0.50

MPC

0.65

ClinPred

0.92

GERP RS

3.4

Varity_R

0.25

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over