NM_014594.3:c.1657G>A

Variant names:

• chr5-179080089-G-A
• rs1445845
• NM_014594.3:c.1657G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595
• Publications: 31 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014594.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF354C	NM_014594.3	MANE Select	c.1657G>A	p.Glu553Lys	missense	Exon 5 of 5	NP_055409.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF354C	ENST00000315475.7	TSL:1 MANE Select	c.1657G>A	p.Glu553Lys	missense	Exon 5 of 5	ENSP00000324064.6

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107094 AN: 151976 Hom.: 37887 Cov.: 33

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

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.: 32 AF XY: 0.693 AC XY: 484849 AN XY: 699970

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

GnomAD4 genome AF: 0.705 AC: 107171 AN: 152094 Hom.: 37912 Cov.: 33 AF XY: 0.710 AC XY: 52784 AN XY: 74344

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	8.9e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N
PhyloP100		0.59
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.035
Sift	Benign	0.24	T
Sift4G	Benign	0.46	T
Polyphen		0.0010	B
Vest4		0.041
MPC		0.13
ClinPred		0.0031	T
GERP RS		2.6
Varity_R		0.045
gMVP		0.16
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1445845; hg19: chr5-178507090; COSMIC: COSV59607473; COSMIC: COSV59607473;