Genetic Variant ZFP30:p.Arg514Gln (chr19-37635000-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001320669.3(ZFP30):c.1541G>A(p.Arg514Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,550,904 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 (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

ZFP30
NM_001320669.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0540

Publications

12 publications found

Variant links:

Genes affected

ZFP30 (HGNC:29555): (ZFP30 zinc finger protein) 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]

ZFP30 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02336815).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320669.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFP30	NM_001320669.3	MANE Select	c.1541G>A	p.Arg514Gln	missense	Exon 6 of 6	NP_001307598.1	D3Y2A0
ZFP30	NM_001320666.3		c.1541G>A	p.Arg514Gln	missense	Exon 6 of 6	NP_001307595.1	D3Y2A0
ZFP30	NM_001320667.3		c.1541G>A	p.Arg514Gln	missense	Exon 6 of 6	NP_001307596.1	Q9Y2G7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFP30	ENST00000684514.1	MANE Select	c.1541G>A	p.Arg514Gln	missense	Exon 6 of 6	ENSP00000508019.1	Q9Y2G7
ZFP30	ENST00000351218.6	TSL:1	c.1541G>A	p.Arg514Gln	missense	Exon 6 of 6	ENSP00000343581.1	Q9Y2G7
ZFP30	ENST00000514101.6	TSL:1	c.1541G>A	p.Arg514Gln	missense	Exon 6 of 6	ENSP00000422930.2	Q9Y2G7

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000358

AC:

AN:

204184

AF XY:

0.000393

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.0000808

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000598

Gnomad FIN exome

AF:

0.00149

Gnomad NFE exome

AF:

0.000400

Gnomad OTH exome

AF:

0.000206

GnomAD4 exome

AF:

0.000221

AC:

309

AN:

1398756

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

148

AN XY:

690304

show subpopulations

African (AFR)

AF:

0.0000644

AC:

AN:

31072

American (AMR)

AF:

0.0000892

AC:

AN:

33616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22140

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39148

South Asian (SAS)

AF:

0.0000397

AC:

AN:

75542

European-Finnish (FIN)

AF:

0.00207

AC:

105

AN:

50754

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5330

European-Non Finnish (NFE)

AF:

0.000161

AC:

175

AN:

1083604

Other (OTH)

AF:

0.000348

AC:

AN:

57550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.000217

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.000212

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000387

AC:

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

0.16

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

0.019

Eigen_PC

Benign

-0.00027

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.80

M_CAP

Benign

0.017

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.5

PhyloP100

-0.054

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.13

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0090

Polyphen

0.91

Vest4

0.22

MVP

0.53

MPC

0.51

ClinPred

0.052

GERP RS

4.0

Varity_R

0.29

gMVP

0.072

Mutation Taster

=94/6

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