19-58455342-A-G

Position:

• chr19-58455342-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207395.3(ZNF324B):​c.398A>G​(p.Glu133Gly) 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. 14/21 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)
• Consequence: ZNF324B NM_207395.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.828

Genes affected

ZNF324B (HGNC:33107): (zinc finger protein 324B) 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13514161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF324B	NM_207395.3	c.398A>G	p.Glu133Gly	missense_variant	4/4	ENST00000336614.9	NP_997278.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF324B	ENST00000336614.9	c.398A>G	p.Glu133Gly	missense_variant	4/4	1	NM_207395.3	ENSP00000337473.3
ZNF324B	ENST00000545523.5	c.398A>G	p.Glu133Gly	missense_variant	5/5	1		ENSP00000438930.1
ZNF324B	ENST00000599193.5	c.398A>G	p.Glu133Gly	missense_variant	4/4	3		ENSP00000473115.1
ZNF324B	ENST00000599194.5	c.398A>G	p.Glu133Gly	missense_variant	4/4	4		ENSP00000472178.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Jun 30, 2024

The c.398A>G (p.E133G) alteration is located in exon 4 (coding exon 3) of the ZNF324B gene. This alteration results from a A to G substitution at nucleotide position 398, causing the glutamic acid (E) at amino acid position 133 to be replaced by a glycine (G). 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	Benign	0.087
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T;T;.;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.73	.;T;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N;N;.;.
REVEL	Benign	0.096
Sift	Benign	0.062	T;T;.;.
Sift4G	Benign	0.15	T;T;D;D
Polyphen		0.88	P;P;.;.
Vest4		0.15
MutPred		0.32		Loss of solvent accessibility (P = 0.0036);Loss of solvent accessibility (P = 0.0036);Loss of solvent accessibility (P = 0.0036);Loss of solvent accessibility (P = 0.0036);
MVP		0.17
MPC		1.8
ClinPred		0.44	T
GERP RS		1.5
Varity_R		0.091
gMVP		0.18

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-58966709;