Variant 5-179080068-T-C 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.1636T>C(p.Phe546Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,584,234 control chromosomes in the GnomAD database, including 381,444 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 ( 37910 hom., cov: 33)

Exomes 𝑓: 0.69 ( 343534 hom. )

Consequence

ZNF354C
NM_014594.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.125778E-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	Protein	UniProt
ZNF354C	NM_014594.3 linkuse as main transcript	c.1636T>C	p.Phe546Leu	missense_variant	5/5	ENST00000315475.7	NP_055409.1	Q86Y25
ZNF354C	XM_017009409.2 linkuse as main transcript	c.1636T>C	p.Phe546Leu	missense_variant	5/5		XP_016864898.1	Q86Y25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF354C	ENST00000315475.7 linkuse as main transcript	c.1636T>C	p.Phe546Leu	missense_variant	5/5	1	NM_014594.3	ENSP00000324064.6		Q86Y25

Frequencies

GnomAD3 genomes

AF:

0.705

AC:

107078

AN:

151944

Hom.:

37885

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:

0.738

GnomAD3 exomes

AF:

0.721

AC:

164068

AN:

227598

Hom.:

59794

AF XY:

0.725

AC XY:

89508

AN XY:

123480

show subpopulations

Gnomad AFR exome

AF:

0.715

Gnomad AMR exome

AF:

0.711

Gnomad ASJ exome

AF:

0.758

Gnomad EAS exome

AF:

0.877

Gnomad SAS exome

AF:

0.837

Gnomad FIN exome

AF:

0.690

Gnomad NFE exome

AF:

0.674

Gnomad OTH exome

AF:

0.725

GnomAD4 exome

AF:

0.690

AC:

987516

AN:

1432172

Hom.:

343534

Cov.:

AF XY:

0.694

AC XY:

494088

AN XY:

712426

show subpopulations

Gnomad4 AFR exome

AF:

0.721

Gnomad4 AMR exome

AF:

0.712

Gnomad4 ASJ exome

AF:

0.747

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:

0.708

GnomAD4 genome

AF:

0.705

AC:

107155

AN:

152062

Hom.:

37910

Cov.:

AF XY:

0.710

AC XY:

52776

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.713

Gnomad4 AMR

AF:

0.730

Gnomad4 ASJ

AF:

0.745

Gnomad4 EAS

AF:

0.889

Gnomad4 SAS

AF:

0.842

Gnomad4 FIN

AF:

0.685

Gnomad4 NFE

AF:

0.669

Gnomad4 OTH

AF:

0.740

Alfa

AF:

0.687

Hom.:

87219

Bravo

AF:

0.707

TwinsUK

AF:

0.667

AC:

2475

ALSPAC

AF:

0.674

AC:

2599

ESP6500AA

AF:

0.716

AC:

3148

ESP6500EA

AF:

0.675

AC:

5797

ExAC

AF:

0.719

AC:

87283

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

0.27

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.023

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.00013

LIST_S2

Benign

0.0054

MetaRNN

Benign

8.1e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.76

REVEL

Benign

0.043

Sift

Benign

0.72

Sift4G

Benign

0.071

Polyphen

0.0

Vest4

0.043

MutPred

0.23

Loss of stability (P = 0.0475);

MPC

0.13

ClinPred

0.0029

GERP RS

1.5

Varity_R

0.056

gMVP

0.046

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