chr5-179080068-T-C

Variant names:

• chr5-179080068-T-C
• rs1445846
• NM_014594.3:c.1636T>C

Variant summary

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

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. 15/21 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 (37910 hom., cov: 33)
  • Exomes 𝑓: 0.69 (343534 hom.)
• Consequence: ZNF354C NM_014594.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 32 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=8.125778E-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.1636T>C	p.Phe546Leu	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.1636T>C	p.Phe546Leu	missense	Exon 5 of 5	ENSP00000324064.6

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107078 AN: 151944 Hom.: 37885 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: 0.738

GnomAD2 exomes AF: 0.721 AC: 164068 AN: 227598 AF XY: 0.725

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 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.: 39 AF XY: 0.694 AC XY: 494088 AN XY: 712426

African (AFR) AF: 0.721 AC: 22911 AN: 31790

American (AMR) AF: 0.712 AC: 27389 AN: 38468

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 18214 AN: 24398

East Asian (EAS) AF: 0.883 AC: 34960 AN: 39600

South Asian (SAS) AF: 0.831 AC: 67798 AN: 81598

European-Finnish (FIN) AF: 0.684 AC: 35981 AN: 52622

Middle Eastern (MID) AF: 0.762 AC: 4266 AN: 5598

European-Non Finnish (NFE) AF: 0.668 AC: 734203 AN: 1099074

Other (OTH) AF: 0.708 AC: 41794 AN: 59024

GnomAD4 genome AF: 0.705 AC: 107155 AN: 152062 Hom.: 37910 Cov.: 33 AF XY: 0.710 AC XY: 52776 AN XY: 74322

African (AFR) AF: 0.713 AC: 29584 AN: 41484

American (AMR) AF: 0.730 AC: 11156 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2584 AN: 3468

East Asian (EAS) AF: 0.889 AC: 4599 AN: 5176

South Asian (SAS) AF: 0.842 AC: 4061 AN: 4822

European-Finnish (FIN) AF: 0.685 AC: 7234 AN: 10556

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45473 AN: 67958

Other (OTH) AF: 0.740 AC: 1558 AN: 2106

Alfa AF: 0.687 Hom.: 153309

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.00013	N
LIST_S2	Benign	0.0054	T
MetaRNN	Benign	8.1e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.14	N
PhyloP100		1.3
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.043
Sift	Benign	0.72	T
Sift4G	Benign	0.071	T
Polyphen		0.0	B
Vest4		0.043
MutPred		0.23		Loss of stability (P = 0.0475)
MPC		0.13
ClinPred		0.0029	T
GERP RS		1.5
Varity_R		0.056
gMVP		0.046
Mutation Taster		=100/0	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: rs1445846; hg19: chr5-178507069; COSMIC: COSV59607467; COSMIC: COSV59607467;