Variant 19-37635000-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 13/21 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

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 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=0.02336815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP30	NM_001320669.3 linkuse as main transcript	c.1541G>A	p.Arg514Gln	missense_variant	6/6	ENST00000684514.1	NP_001307598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZFP30	ENST00000684514.1 linkuse as main transcript	c.1541G>A	p.Arg514Gln	missense_variant	6/6		NM_001320669.3	ENSP00000508019.1	Q9Y2G7
ZFP30	ENST00000351218.6 linkuse as main transcript	c.1541G>A	p.Arg514Gln	missense_variant	6/6	1		ENSP00000343581.1	Q9Y2G7
ZFP30	ENST00000514101.6 linkuse as main transcript	c.1541G>A	p.Arg514Gln	missense_variant	6/6	1		ENSP00000422930.2	Q9Y2G7
ZFP30	ENST00000589018.5 linkuse as main transcript	c.232+8265G>A		intron_variant		5		ENSP00000467387.1	K7EPH5

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

GnomAD3 exomes

AF:

0.000358

AC:

AN:

204184

Hom.:

AF XY:

0.000393

AC XY:

AN XY:

109554

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.0000644

Gnomad4 AMR exome

AF:

0.0000892

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000397

Gnomad4 FIN exome

AF:

0.00207

Gnomad4 NFE exome

AF:

0.000161

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000217

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000213

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000387

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.1541G>A (p.R514Q) alteration is located in exon 6 (coding exon 4) of the ZFP30 gene. This alteration results from a G to A substitution at nucleotide position 1541, causing the arginine (R) at amino acid position 514 to be replaced by a glutamine (Q). 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

0.16

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

0.019

Eigen_PC

Benign

-0.00027

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.91

P;P

Vest4

0.22

MVP

0.53

MPC

0.51

ClinPred

0.052

GERP RS

4.0

Varity_R

0.29

gMVP

0.072

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