NM_014594.3:c.256A>C

Variant names:

• chr5-179078688-A-C
• NM_014594.3:c.256A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014594.3(ZNF354C):​c.256A>C​(p.Lys86Gln) 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. 16/22 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: 1.07
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089767486).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF354C	NM_014594.3	MANE Select	c.256A>C	p.Lys86Gln	missense	Exon 5 of 5	NP_055409.1	Q86Y25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF354C	ENST00000315475.7	TSL:1 MANE Select	c.256A>C	p.Lys86Gln	missense	Exon 5 of 5	ENSP00000324064.6	Q86Y25
	ZNF354C	ENST00000911395.1		c.262A>C	p.Lys88Gln	missense	Exon 5 of 5	ENSP00000581454.1
	ZNF354C	ENST00000911394.1		c.256A>C	p.Lys86Gln	missense	Exon 5 of 5	ENSP00000581453.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.1
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.014
Sift	Benign	0.058	T
Sift4G	Benign	0.21	T
Polyphen		0.046	B
Vest4		0.066
MutPred		0.42		Loss of ubiquitination at K86 (P = 0.0092)
MVP		0.21
MPC		0.12
ClinPred		0.052	T
GERP RS		1.6
Varity_R		0.064
gMVP		0.12
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

hg19: chr5-178505689;