Genetic Variant ZNF347:p.Glu629Lys (chr19-53140943-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032584.3(ZNF347):c.1885G>A(p.Glu629Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. E629A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

ZNF347
NM_032584.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.45

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13053867).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032584.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF347	NM_032584.3	MANE Select	c.1885G>A	p.Glu629Lys	missense	Exon 5 of 5	NP_115973.2	Q96SE7-1
ZNF347	NM_001172674.2		c.1888G>A	p.Glu630Lys	missense	Exon 5 of 5	NP_001166145.1	Q96SE7-2
ZNF347	NM_001172675.2		c.1888G>A	p.Glu630Lys	missense	Exon 5 of 5	NP_001166146.1	Q96SE7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF347	ENST00000334197.12	TSL:1 MANE Select	c.1885G>A	p.Glu629Lys	missense	Exon 5 of 5	ENSP00000334146.6	Q96SE7-1
ZNF347	ENST00000452676.6	TSL:2	c.1888G>A	p.Glu630Lys	missense	Exon 5 of 5	ENSP00000405218.2	Q96SE7-2
ZNF347	ENST00000601469.2	TSL:2	c.1888G>A	p.Glu630Lys	missense	Exon 5 of 5	ENSP00000471712.2	Q96SE7-2

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151382

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251260

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000889

AC:

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111964

Other (OTH)

AF:

0.0000331

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151504

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74004

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41212

American (AMR)

AF:

0.00

AC:

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67946

Other (OTH)

AF:

0.00

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.32

M_CAP

Benign

0.0029

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-1.5

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.056

Sift

Uncertain

0.029

Sift4G

Uncertain

0.031

Polyphen

0.13

Vest4

0.16

MVP

0.33

MPC

0.017

ClinPred

0.067

GERP RS

1.8

Varity_R

0.14

gMVP

0.063

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over