Genetic Variant ZNF347:p.Cys711Tyr (chr19-53140696-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_032584.3(ZNF347):c.2132G>A(p.Cys711Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZNF347
NM_032584.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF347	NM_032584.3 link	c.2132G>A	p.Cys711Tyr	missense_variant	Exon 5 of 5	ENST00000334197.12	NP_115973.2	Q96SE7-1
ZNF347	NM_001172674.2 link	c.2135G>A	p.Cys712Tyr	missense_variant	Exon 5 of 5		NP_001166145.1	Q96SE7-2A0A024R4L7
ZNF347	NM_001172675.2 link	c.2135G>A	p.Cys712Tyr	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.2132G>A	p.Cys711Tyr	missense_variant	Exon 5 of 5	1	NM_032584.3	ENSP00000334146.6	Q96SE7-1
ZNF347	ENST00000452676.6 link	c.2135G>A	p.Cys712Tyr	missense_variant	Exon 5 of 5	2		ENSP00000405218.2	Q96SE7-2
ZNF347	ENST00000601469.2 link	c.2135G>A	p.Cys712Tyr	missense_variant	Exon 5 of 5	2		ENSP00000471712.2	Q96SE7-2
ZNF347	ENST00000601804.5 link	c.97+7985G>A		intron_variant	Intron 3 of 3	4		ENSP00000470590.1	M0QZJ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251122

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135716

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727128

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000413

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2135G>A (p.C712Y) 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 2135, causing the cysteine (C) at amino acid position 712 to be replaced by a tyrosine (Y). 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

0.77

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Uncertain

0.53

D;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.28

LIST_S2

Uncertain

0.88

D;D;.

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Uncertain

-0.19

MutationAssessor

Pathogenic

3.5

H;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-9.9

D;D;.

REVEL

Benign

0.24

Sift

Uncertain

0.024

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.20

MutPred

0.74

Gain of phosphorylation at C711 (P = 0.042);.;.;

MVP

0.78

MPC

0.094

ClinPred

0.82

GERP RS

-2.8

Varity_R

0.38

gMVP

0.23

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