Genetic Variant NM_138347.5:c.620G>C (chr19-57686895-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138347.5(ZNF551):c.620G>C(p.Ser207Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,614,212 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

ZNF551
NM_138347.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.41

Publications

4 publications found

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:

ENSG00000269026 (HGNC:):

ENSG00000269026 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014395207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF551	NM_138347.5 link	c.620G>C	p.Ser207Thr	missense_variant	Exon 3 of 3	ENST00000282296.10	NP_612356.2	Q7Z340-1
ZNF551	NM_001270938.2 link	c.536G>C	p.Ser179Thr	missense_variant	Exon 3 of 3		NP_001257867.1	Q7Z340
ZNF551	NR_073102.2 link	n.683G>C		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF551	ENST00000282296.10 link	c.620G>C	p.Ser207Thr	missense_variant	Exon 3 of 3	1	NM_138347.5	ENSP00000282296.5		Q7Z340-1
ENSG00000269026	ENST00000594684.1 link	c.33+4651G>C		intron_variant	Intron 1 of 2	1		ENSP00000472160.1		M0R1X1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000255

AC:

AN:

251058

AF XY:

0.000191

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00219

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000222

AC:

325

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000217

AC XY:

158

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33480

American (AMR)

AF:

0.000492

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00184

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000192

AC:

213

AN:

1112010

Other (OTH)

AF:

0.000364

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000223

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41574

American (AMR)

AF:

0.000392

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000336

Hom.:

Bravo

AF:

0.000283

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000189

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.572G>C (p.S191T) alteration is located in exon 3 (coding exon 3) of the ZNF551 gene. This alteration results from a G to C substitution at nucleotide position 572, causing the serine (S) at amino acid position 191 to be replaced by a threonine (T). 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

0.067

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.4

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00018

LIST_S2

Benign

0.029

T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L

PhyloP100

-1.4

PrimateAI

Benign

0.20

REVEL

Benign

0.012

Sift4G

Benign

0.33

T;T

Polyphen

0.017

.;B

Vest4

0.085

MVP

0.16

MPC

0.16

ClinPred

0.011

GERP RS

0.47

Varity_R

0.056

gMVP

0.0061

Mutation Taster

=100/0

polymorphism

(source)

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

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NM_138347.5:c.620G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over