NM_014347.3:c.525A>C

Variant names:

• chr19-58471017-A-C
• rs10418774
• NM_014347.3:c.525A>C

Variant summary

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

The NM_014347.3(ZNF324):​c.525A>C​(p.Arg175Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZNF324 NM_014347.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 13 publications found

Genes affected

ZNF324 (HGNC:14096): (zinc finger protein 324) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Acts upstream of or within with a positive effect on G1/S transition of mitotic cell cycle and cell population proliferation. Predicted to be active in nucleus. [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=0.09662816).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014347.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF324	NM_014347.3	MANE Select	c.525A>C	p.Arg175Ser	missense	Exon 4 of 4	NP_055162.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF324	ENST00000196482.4	TSL:1 MANE Select	c.525A>C	p.Arg175Ser	missense	Exon 4 of 4	ENSP00000196482.3
	ZNF324	ENST00000536459.6	TSL:2	c.525A>C	p.Arg175Ser	missense	Exon 4 of 4	ENSP00000444812.1
	ZNF324	ENST00000593925.1	TSL:2	c.99A>C	p.Arg33Ser	missense	Exon 1 of 2	ENSP00000471778.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 111

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.25
DANN	Benign	0.72
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		-2.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.047
Sift	Benign	0.15	T
Sift4G	Benign	0.44	T
Polyphen		0.28	B
Vest4		0.15
MutPred		0.50		Gain of phosphorylation at R175 (P = 0.0186)
MVP		0.18
MPC		0.76
ClinPred		0.081	T
GERP RS		-2.6
PromoterAI		0.038	Neutral
Varity_R		0.070
gMVP		0.16
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs10418774; hg19: chr19-58982384;