19-58470940-G-C

Variant names:

• chr19-58470940-G-C
• rs2053025074
• NM_014347.3:c.448G>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.448G>C​(p.Gly150Arg) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G150S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF324 NM_014347.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 0 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=0.16377792).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF324	NM_014347.3	MANE Select	c.448G>C	p.Gly150Arg	missense	Exon 4 of 4	NP_055162.1	O75467

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF324	ENST00000196482.4	TSL:1 MANE Select	c.448G>C	p.Gly150Arg	missense	Exon 4 of 4	ENSP00000196482.3	O75467
	ZNF324	ENST00000536459.6	TSL:2	c.448G>C	p.Gly150Arg	missense	Exon 4 of 4	ENSP00000444812.1	O75467
	ZNF324	ENST00000868897.1		c.448G>C	p.Gly150Arg	missense	Exon 3 of 3	ENSP00000538956.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.14
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.25		Gain of MoRF binding (P = 0.0041)
MVP		0.39
MPC		0.89
ClinPred		0.60	D
GERP RS		3.3
PromoterAI		0.024	Neutral
Varity_R		0.11
gMVP		0.045
Mutation Taster		=90/10	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: rs2053025074; hg19: chr19-58982307;