Variant 5-179080089-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ZNF354C	NM_014594.3 linkuse as main transcript	c.1657G>A	p.Glu553Lys	missense_variant	5/5	ENST00000315475.7
ZNF354C	XM_017009409.2 linkuse as main transcript	c.1657G>A	p.Glu553Lys	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF354C	ENST00000315475.7 linkuse as main transcript	c.1657G>A	p.Glu553Lys	missense_variant	5/5	1	NM_014594.3	P1

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

GnomAD3 exomes

AF:

0.720

AC:

150927

AN:

209540

Hom.:

54929

AF XY:

0.724

AC XY:

81927

AN XY:

113222

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 SAS exome

AF:

0.838

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

Gnomad4 AFR exome

AF:

0.721

Gnomad4 AMR exome

AF:

0.713

Gnomad4 ASJ exome

AF:

0.746

Gnomad4 EAS exome

AF:

0.883

Gnomad4 SAS exome

AF:

0.831

Gnomad4 FIN exome

AF:

0.684

Gnomad4 NFE exome

AF:

0.668

Gnomad4 OTH exome

AF:

0.707

GnomAD4 genome

AF:

0.705

AC:

107171

AN:

152094

Hom.:

37912

Cov.:

AF XY:

0.710

AC XY:

52784

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.713

Gnomad4 AMR

AF:

0.730

Gnomad4 ASJ

AF:

0.745

Gnomad4 EAS

AF:

0.888

Gnomad4 SAS

AF:

0.842

Gnomad4 FIN

AF:

0.685

Gnomad4 NFE

AF:

0.669

Gnomad4 OTH

AF:

0.739

Alfa

AF:

0.684

Hom.:

80716

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

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

MutationTaster

Benign

1.0

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over