5-178713541-T-A

Position:

• chr5-178713541-T-A

Variant summary

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

The NM_005649.3(ZNF354A):​c.337A>T​(p.Asn113Tyr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF354A NM_005649.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.201

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07153177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF354A	NM_005649.3	c.337A>T	p.Asn113Tyr	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.337A>T	p.Asn113Tyr	missense_variant	5/5	1	NM_005649.3	ENSP00000337122.2
ZNF354A	ENST00000520331.5	c.337A>T	p.Asn113Tyr	missense_variant	4/4	1		ENSP00000429675.1
ENSG00000285978	ENST00000638723.1	n.257-6369A>T		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

Feb 05, 2024

The c.337A>T (p.N113Y) alteration is located in exon 5 (coding exon 4) of the ZNF354A gene. This alteration results from a A to T substitution at nucleotide position 337, causing the asparagine (N) at amino acid position 113 to be replaced by a tyrosine (Y). 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	0.087
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.039	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.00056	N
LIST_S2	Benign	0.35	T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.96	N;N
REVEL	Benign	0.021
Sift	Uncertain	0.013	D;T
Sift4G	Uncertain	0.055	T;D
Polyphen		0.0040	B;.
Vest4		0.14
MutPred		0.30		Loss of disorder (P = 0.0486);Loss of disorder (P = 0.0486);
MVP		0.088
MPC		0.26
ClinPred		0.030	T
GERP RS		2.1
Varity_R		0.034
gMVP		0.13

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: chr5-178140542;