5-178713154-A-G

Position:

• chr5-178713154-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005649.3(ZNF354A):​c.724T>C​(p.Phe242Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF354A NM_005649.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.83

Genes affected

ZNF354A (HGNC:11628): (zinc finger protein 354A) 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 cytosol; nucleolus; and nucleoplasm. Biomarker of in situ carcinoma and seminoma. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285978 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37501973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF354A	NM_005649.3	c.724T>C	p.Phe242Leu	missense_variant	5/5	ENST00000335815.7	NP_005640.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF354A	ENST00000335815.7	c.724T>C	p.Phe242Leu	missense_variant	5/5	1	NM_005649.3	ENSP00000337122.2
ENSG00000285978	ENST00000638723.1	n.257-5982T>C		intron_variant		5		ENSP00000492050.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Jan 05, 2022

The c.724T>C (p.F242L) alteration is located in exon 5 (coding exon 4) of the ZNF354A gene. This alteration results from a T to C substitution at nucleotide position 724, causing the phenylalanine (F) at amino acid position 242 to be replaced by a leucine (L). 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	Pathogenic	0.95
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.22
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.30
MutPred		0.56		Loss of ubiquitination at K245 (P = 0.1264);
MVP		0.45
MPC		0.83
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.45
gMVP		0.18

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: chr5-178140155;