dbSNP rs1445845: ZNF354C:p.Glu553Lys (chr5-179080089-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014594.3(ZNF354C):c.1657G>A(p.Glu553Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,561,944 control chromosomes in the GnomAD database, including 375,343 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.70 ( 37912 hom., cov: 33)

Exomes 𝑓: 0.69 ( 337431 hom. )

Consequence

ZNF354C
NM_014594.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.595

Publications

31 publications found

Variant links:

Genes affected

ZNF354C (HGNC:16736): (zinc finger protein 354C) 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. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF354C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.8721475E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF354C	NM_014594.3 link	c.1657G>A	p.Glu553Lys	missense_variant	Exon 5 of 5	ENST00000315475.7	NP_055409.1	Q86Y25
ZNF354C	XM_017009409.2 link	c.1657G>A	p.Glu553Lys	missense_variant	Exon 5 of 5		XP_016864898.1	Q86Y25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF354C	ENST00000315475.7 link	c.1657G>A	p.Glu553Lys	missense_variant	Exon 5 of 5	1	NM_014594.3	ENSP00000324064.6		Q86Y25

Frequencies

GnomAD3 genomes

AF:

0.705

AC:

107094

AN:

151976

Hom.:

37887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.713

Gnomad AMI

AF:

0.754

Gnomad AMR

AF:

0.730

Gnomad ASJ

AF:

0.745

Gnomad EAS

AF:

0.888

Gnomad SAS

AF:

0.844

Gnomad FIN

AF:

0.685

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.669

Gnomad OTH

AF:

0.737

GnomAD2 exomes

AF:

0.720

AC:

150927

AN:

209540

AF XY:

0.724

show subpopulations

Gnomad AFR exome

AF:

0.715

Gnomad AMR exome

AF:

0.712

Gnomad ASJ exome

AF:

0.759

Gnomad EAS exome

AF:

0.876

Gnomad FIN exome

AF:

0.691

Gnomad NFE exome

AF:

0.674

Gnomad OTH exome

AF:

0.729

GnomAD4 exome

AF:

0.689

AC:

971127

AN:

1409850

Hom.:

337431

Cov.:

AF XY:

0.693

AC XY:

484849

AN XY:

699970

show subpopulations

African (AFR)

AF:

0.721

AC:

22517

AN:

31238

American (AMR)

AF:

0.713

AC:

25058

AN:

35162

Ashkenazi Jewish (ASJ)

AF:

0.746

AC:

17062

AN:

22864

East Asian (EAS)

AF:

0.883

AC:

34896

AN:

39530

South Asian (SAS)

AF:

0.831

AC:

64280

AN:

77362

European-Finnish (FIN)

AF:

0.684

AC:

35389

AN:

51726

Middle Eastern (MID)

AF:

0.763

AC:

4173

AN:

5472

European-Non Finnish (NFE)

AF:

0.668

AC:

726585

AN:

1088306

Other (OTH)

AF:

0.707

AC:

41167

AN:

58190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

13109

26218

39327

52436

65545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19024

38048

57072

76096

95120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.705

AC:

107171

AN:

152094

Hom.:

37912

Cov.:

AF XY:

0.710

AC XY:

52784

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.713

AC:

29593

AN:

41494

American (AMR)

AF:

0.730

AC:

11161

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.745

AC:

2583

AN:

3466

East Asian (EAS)

AF:

0.888

AC:

4598

AN:

5176

South Asian (SAS)

AF:

0.842

AC:

4063

AN:

4824

European-Finnish (FIN)

AF:

0.685

AC:

7243

AN:

10568

Middle Eastern (MID)

AF:

0.748

AC:

220

AN:

294

European-Non Finnish (NFE)

AF:

0.669

AC:

45464

AN:

67956

Other (OTH)

AF:

0.739

AC:

1560

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1665

3330

4995

6660

8325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.688

Hom.:

116960

Bravo

AF:

0.707

TwinsUK

AF:

0.667

AC:

2474

ALSPAC

AF:

0.674

AC:

2599

ESP6500AA

AF:

0.720

AC:

3146

ESP6500EA

AF:

0.677

AC:

5811

ExAC

AF:

0.719

AC:

87068

Asia WGS

AF:

0.848

AC:

2948

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.33

MetaRNN

Benign

8.9e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

PhyloP100

0.59

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.95

REVEL

Benign

0.035

Sift

Benign

0.24

Sift4G

Benign

0.46

Polyphen

0.0010

Vest4

0.041

MPC

0.13

ClinPred

0.0031

GERP RS

2.6

Varity_R

0.045

gMVP

0.16

Mutation Taster

=97/3

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over