Variant 19-56553996-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_020828.2(ZFP28):c.1211G>A(p.Ser404Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,332 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZFP28
NM_020828.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20

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:55272): (ZNF470 divergent transcript)

ZNF470-DT links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02380982).

BP6

Variant 19-56553996-G-A is Benign according to our data. Variant chr19-56553996-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3334448.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZFP28	NM_020828.2 linkuse as main transcript	c.1211G>A	p.Ser404Asn	missense_variant	8/8	ENST00000301318.8	NP_065879.1
ZNF470-DT	XM_047439806.1 linkuse as main transcript	c.*11-6725C>T		intron_variant			XP_047295762.1
ZFP28	XM_011526463.4 linkuse as main transcript	c.1184G>A	p.Ser395Asn	missense_variant	8/8		XP_011524765.2
ZFP28	XM_011526462.4 linkuse as main transcript	c.920G>A	p.Ser307Asn	missense_variant	8/8		XP_011524764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP28	ENST00000301318.8 linkuse as main transcript	c.1211G>A	p.Ser404Asn	missense_variant	8/8	1	NM_020828.2	ENSP00000301318	P1	Q8NHY6-1
ZNF470-DT	ENST00000596587.2 linkuse as main transcript	n.370-6725C>T		intron_variant, non_coding_transcript_variant		1
ZNF470-DT	ENST00000670254.1 linkuse as main transcript	n.454-6725C>T		intron_variant, non_coding_transcript_variant
ZNF470-DT	ENST00000702092.1 linkuse as main transcript	n.292-6725C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459332

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725928

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.052

DANN

Benign

0.13

DEOGEN2

Benign

0.015

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.014

M_CAP

Benign

0.0027

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.045

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

0.44

REVEL

Benign

0.0040

Sift

Benign

1.0

Sift4G

Benign

0.92

Polyphen

0.0

Vest4

0.015

MutPred

0.25

Loss of disorder (P = 0.1243);

MVP

0.18

MPC

0.16

ClinPred

0.022

GERP RS

-5.8

Varity_R

0.035

gMVP

0.024

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over