5-179080068-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014594.3(ZNF354C):​c.1636T>A​(p.Phe546Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 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 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06022805).

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>A	p.Phe546Ile	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>A	p.Phe546Ile	missense	Exon 5 of 5	ENSP00000324064.6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152020 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1437072 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 714620

African (AFR) AF: 0.00 AC: 0 AN: 31844

American (AMR) AF: 0.00 AC: 0 AN: 38506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24432

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.00 AC: 0 AN: 81724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103502

Other (OTH) AF: 0.00 AC: 0 AN: 59198

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152020 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74232

African (AFR) AF: 0.00 AC: 0 AN: 41384

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 153309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.038
Sift	Benign	0.16	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.0	B
Vest4		0.19
MutPred		0.42		Loss of stability (P = 0.0486)
MVP		0.081
MPC		0.16
ClinPred		0.11	T
GERP RS		1.5
Varity_R		0.064
gMVP		0.067
Mutation Taster		=100/0	polymorphism

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;