Genetic Variant ZNF347:p.Gly687Asp (chr19-53140768-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032584.3(ZNF347):c.2060G>A(p.Gly687Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF347
NM_032584.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.175

Variant links:

Genes affected

ZNF347 (HGNC:16447): (zinc finger protein 347) Predicted to enable DNA-binding transcription factor 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]

ZNF347 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.12484014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF347	NM_032584.3 link	c.2060G>A	p.Gly687Asp	missense_variant	Exon 5 of 5	ENST00000334197.12	NP_115973.2	Q96SE7-1
ZNF347	NM_001172674.2 link	c.2063G>A	p.Gly688Asp	missense_variant	Exon 5 of 5		NP_001166145.1	Q96SE7-2A0A024R4L7
ZNF347	NM_001172675.2 link	c.2063G>A	p.Gly688Asp	missense_variant	Exon 5 of 5		NP_001166146.1	Q96SE7-2A0A024R4L7A8K1S9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF347	ENST00000334197.12 link	c.2060G>A	p.Gly687Asp	missense_variant	Exon 5 of 5	1	NM_032584.3	ENSP00000334146.6	Q96SE7-1
ZNF347	ENST00000452676.6 link	c.2063G>A	p.Gly688Asp	missense_variant	Exon 5 of 5	2		ENSP00000405218.2	Q96SE7-2
ZNF347	ENST00000601469.2 link	c.2063G>A	p.Gly688Asp	missense_variant	Exon 5 of 5	2		ENSP00000471712.2	Q96SE7-2
ZNF347	ENST00000601804.5 link	c.97+7913G>A		intron_variant	Intron 3 of 3	4		ENSP00000470590.1	M0QZJ6

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249442

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460186

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726320

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2063G>A (p.G688D) alteration is located in exon 5 (coding exon 4) of the ZNF347 gene. This alteration results from a G to A substitution at nucleotide position 2063, causing the glycine (G) at amino acid position 688 to be replaced by an aspartic acid (D). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.53

T;T;.

M_CAP

Benign

0.0032

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.79

N;.;.

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-4.2

D;D;.

REVEL

Benign

0.043

Sift

Benign

0.17

T;T;.

Sift4G

Uncertain

0.038

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.15

MutPred

0.58

Loss of MoRF binding (P = 0.0381);.;.;

MVP

0.22

MPC

0.089

ClinPred

0.65

GERP RS

1.5

Varity_R

0.24

gMVP

0.021

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over