5-179078955-C-A

Position:

• chr5-179078955-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014594.3(ZNF354C):​c.523C>A​(p.Leu175Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF354C NM_014594.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.184

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18488318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF354C	NM_014594.3	c.523C>A	p.Leu175Ile	missense_variant	5/5	ENST00000315475.7	NP_055409.1
ZNF354C	XM_017009409.2	c.523C>A	p.Leu175Ile	missense_variant	5/5		XP_016864898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF354C	ENST00000315475.7	c.523C>A	p.Leu175Ile	missense_variant	5/5	1	NM_014594.3	ENSP00000324064.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.523C>A (p.L175I) alteration is located in exon 5 (coding exon 4) of the ZNF354C gene. This alteration results from a C to A substitution at nucleotide position 523, causing the leucine (L) at amino acid position 175 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.095
Sift	Benign	0.13	T
Sift4G	Benign	0.099	T
Polyphen		0.46	P
Vest4		0.061
MutPred		0.65		Loss of stability (P = 0.0827);
MVP		0.19
MPC		0.13
ClinPred		0.15	T
GERP RS		3.3
Varity_R		0.092
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-178505956;