Genetic Variant ZNF347:p.Ala669Thr (chr19-53140823-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032584.3(ZNF347):c.2005G>A(p.Ala669Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZNF347
NM_032584.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.79

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 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=0.028025389).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF347	NM_032584.3 link	c.2005G>A	p.Ala669Thr	missense_variant	Exon 5 of 5	ENST00000334197.12	NP_115973.2	Q96SE7-1
ZNF347	NM_001172674.2 link	c.2008G>A	p.Ala670Thr	missense_variant	Exon 5 of 5		NP_001166145.1	Q96SE7-2A0A024R4L7
ZNF347	NM_001172675.2 link	c.2008G>A	p.Ala670Thr	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.2005G>A	p.Ala669Thr	missense_variant	Exon 5 of 5	1	NM_032584.3	ENSP00000334146.6	Q96SE7-1
ZNF347	ENST00000452676.6 link	c.2008G>A	p.Ala670Thr	missense_variant	Exon 5 of 5	2		ENSP00000405218.2	Q96SE7-2
ZNF347	ENST00000601469.2 link	c.2008G>A	p.Ala670Thr	missense_variant	Exon 5 of 5	2		ENSP00000471712.2	Q96SE7-2
ZNF347	ENST00000601804.5 link	c.97+7858G>A		intron_variant	Intron 3 of 3	4		ENSP00000470590.1	M0QZJ6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152160

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:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251042

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461624

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000384

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2008G>A (p.A670T) 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 2008, causing the alanine (A) at amino acid position 670 to be replaced by a threonine (T). 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

0.13

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.8

DANN

Benign

0.50

DEOGEN2

Benign

0.011

T;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.54

T;T;.

M_CAP

Benign

0.0016

MetaRNN

Benign

0.028

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.79

N;.;.

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.61

N;N;.

REVEL

Benign

0.0080

Sift

Benign

0.58

T;T;.

Sift4G

Benign

0.77

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.014

MutPred

0.30

Gain of disorder (P = 0.0593);.;.;

MVP

0.11

MPC

0.013

ClinPred

0.014

GERP RS

-5.9

Varity_R

0.023

gMVP

0.025

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