chr19-56553947-T-G

Position:

chr19-56553947-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000301318.8(ZFP28):c.1162T>G(p.Ser388Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ZFP28
ENST00000301318.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.224

Variant links:

Genes affected

ZFP28 (HGNC:17801): (ZFP28 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]

ZFP28 links:

ZNF470-DT (HGNC:):

ZNF470-DT links:

ZNF470-DT (HGNC:55272): (ZNF470 divergent transcript)

ZNF470-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.093580216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP28	NM_020828.2 linkuse as main transcript	c.1162T>G	p.Ser388Ala	missense_variant	8/8	ENST00000301318.8	NP_065879.1	Q8NHY6-1
ZFP28	XM_011526463.4 linkuse as main transcript	c.1135T>G	p.Ser379Ala	missense_variant	8/8		XP_011524765.2
ZFP28	XM_011526462.4 linkuse as main transcript	c.871T>G	p.Ser291Ala	missense_variant	8/8		XP_011524764.1
ZNF470-DT	XM_047439806.1 linkuse as main transcript	c.*11-6676A>C		intron_variant			XP_047295762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZFP28	ENST00000301318.8 linkuse as main transcript	c.1162T>G	p.Ser388Ala	missense_variant	8/8	1	NM_020828.2	ENSP00000301318.3	Q8NHY6-1
ZNF470-DT	ENST00000596587.2 linkuse as main transcript	n.370-6676A>C		intron_variant		1
ZNF470-DT	ENST00000670254.1 linkuse as main transcript	n.454-6676A>C		intron_variant
ZNF470-DT	ENST00000702092.1 linkuse as main transcript	n.292-6676A>C		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250284

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461106

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726826

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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:

0.0000108

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.1162T>G (p.S388A) alteration is located in exon 8 (coding exon 8) of the ZFP28 gene. This alteration results from a T to G substitution at nucleotide position 1162, causing the serine (S) at amino acid position 388 to be replaced by an alanine (A). 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

0.080

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.4

DANN

Benign

0.86

DEOGEN2

Benign

0.031

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.054

M_CAP

Benign

0.0048

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.98

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.95

REVEL

Benign

0.024

Sift

Benign

0.20

Sift4G

Benign

0.92

Polyphen

0.30

Vest4

0.14

MutPred

0.39

Loss of disorder (P = 0.0404);

MVP

0.29

MPC

0.26

ClinPred

0.098

GERP RS

3.0

Varity_R

0.081

gMVP

0.036

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