Variant 19-57687037-C-A 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_138347.5(ZNF551):c.762C>A(p.Ser254Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,614,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZNF551
NM_138347.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.45

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 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=0.038632423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF551	NM_138347.5 linkuse as main transcript	c.762C>A	p.Ser254Arg	missense_variant	3/3	ENST00000282296.10	NP_612356.2
ZNF551	NM_001270938.2 linkuse as main transcript	c.678C>A	p.Ser226Arg	missense_variant	3/3		NP_001257867.1
ZNF551	NR_073102.2 linkuse as main transcript	n.825C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF551	ENST00000282296.10 linkuse as main transcript	c.762C>A	p.Ser254Arg	missense_variant	3/3	1	NM_138347.5	ENSP00000282296	P1	Q7Z340-1
ZNF551	ENST00000601064.1 linkuse as main transcript	c.678C>A	p.Ser226Arg	missense_variant	3/3	1		ENSP00000472674
ZNF551	ENST00000596085.1 linkuse as main transcript	c.157+1652C>A		intron_variant		2		ENSP00000472230

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251450

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727246

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:

0.00000270

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000947

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.00462

AC:

AN:

3478

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 18, 2023

The c.714C>A (p.S238R) alteration is located in exon 3 (coding exon 3) of the ZNF551 gene. This alteration results from a C to A substitution at nucleotide position 714, causing the serine (S) at amino acid position 238 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

0.21

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.98

DANN

Benign

0.55

DEOGEN2

Benign

0.057

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00020

LIST_S2

Benign

0.30

T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

REVEL

Benign

0.012

Sift4G

Benign

0.15

T;T

Polyphen

0.17

.;B

Vest4

0.14

MutPred

0.22

.;Loss of ubiquitination at K258 (P = 0.0517);

MVP

0.11

MPC

0.18

ClinPred

0.049

GERP RS

-3.5

Varity_R

0.081

gMVP

0.0037

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