Variant chr19-57682243-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_138347.5(ZNF551):c.80A>G(p.Gln27Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ZNF551
NM_138347.5 missense, splice_region

Scores

Splicing: ADA: 0.2574

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.697

Variant links:

Genes affected

ZNF551 (HGNC:25108): (zinc finger protein 551) 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]

ZNF551 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=0.20577088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF551	NM_138347.5 linkuse as main transcript	c.80A>G	p.Gln27Arg	missense_variant, splice_region_variant	1/3	ENST00000282296.10	NP_612356.2
ZNF551	NM_001270938.2 linkuse as main transcript	c.-4+121A>G		intron_variant			NP_001257867.1
ZNF551	NR_073102.2 linkuse as main transcript	n.267A>G		splice_region_variant, non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF551	ENST00000282296.10 linkuse as main transcript	c.80A>G	p.Gln27Arg	missense_variant, splice_region_variant	1/3	1	NM_138347.5	ENSP00000282296	P1	Q7Z340-1
ZNF551	ENST00000601064.1 linkuse as main transcript	c.-4+121A>G		intron_variant		1		ENSP00000472674
ZNF551	ENST00000599402.1 linkuse as main transcript	n.237A>G		splice_region_variant, non_coding_transcript_exon_variant	1/2	1
ZNF551	ENST00000596085.1 linkuse as main transcript	c.32A>G	p.Gln11Arg	missense_variant, splice_region_variant	1/3	2		ENSP00000472230

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1398016

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689546

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:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

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 08, 2023

The c.32A>G (p.Q11R) alteration is located in exon 1 (coding exon 1) of the ZNF551 gene. This alteration results from a A to G substitution at nucleotide position 32, causing the glutamine (Q) at amino acid position 11 to be replaced by an arginine (R). 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

0.079

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.011

T;.;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.0085

LIST_S2

Benign

0.027

T;T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.49

REVEL

Benign

0.12

Sift4G

Benign

0.079

T;T;D

Polyphen

0.64

P;.;.

Vest4

0.16

MutPred

0.45

Gain of solvent accessibility (P = 0.0055);.;.;

MVP

0.32

MPC

0.071

ClinPred

0.83

GERP RS

0.17

Varity_R

0.053

gMVP

0.087

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.26

dbscSNV1_RF

Benign

0.52

SpliceAI score (max)

0.030

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