5-179079145-A-T

Position:

• chr5-179079145-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014594.3(ZNF354C):​c.713A>T​(p.His238Leu) 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 pathogenic 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: 2.74

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF354C	NM_014594.3	c.713A>T	p.His238Leu	missense_variant	5/5	ENST00000315475.7	NP_055409.1
ZNF354C	XM_017009409.2	c.713A>T	p.His238Leu	missense_variant	5/5		XP_016864898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF354C	ENST00000315475.7	c.713A>T	p.His238Leu	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

Sep 01, 2021

The c.713A>T (p.H238L) alteration is located in exon 5 (coding exon 4) of the ZNF354C gene. This alteration results from a A to T substitution at nucleotide position 713, causing the histidine (H) at amino acid position 238 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	0.84
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.10	T
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Pathogenic	3.5	M
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-11	D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.75		Loss of disorder (P = 0.0551);
MVP		0.93
MPC		0.61
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.77
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr5-178506146;