chr19-58470891-G-T

Variant names:

• chr19-58470891-G-T
• rs1323670824
• NM_014347.3:c.399G>T

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.399G>T​(p.Glu133Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF324 NM_014347.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• 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=0.17599696).

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.399G>T	p.Glu133Asp	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.399G>T	p.Glu133Asp	missense	Exon 4 of 4	ENSP00000196482.3	O75467
	ZNF324	ENST00000536459.6	TSL:2	c.399G>T	p.Glu133Asp	missense	Exon 4 of 4	ENSP00000444812.1	O75467
	ZNF324	ENST00000868897.1		c.399G>T	p.Glu133Asp	missense	Exon 3 of 3	ENSP00000538956.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461892 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

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	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.6
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.047
Sift	Benign	0.16	T
Sift4G	Benign	0.31	T
Polyphen		0.74	P
Vest4		0.25
MutPred		0.20		Loss of methylation at K135 (P = 0.1103)
MVP		0.28
MPC		1.2
ClinPred		0.69	D
GERP RS		3.4
PromoterAI		-0.0015	Neutral
Varity_R		0.13
gMVP		0.067
Mutation Taster		=92/8	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: rs1323670824; hg19: chr19-58982258;