dbSNP rs577858846: ZNF324:p.Ala156Asp (chr19-58470959-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014347.3(ZNF324):c.467C>A(p.Ala156Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A156G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF324
NM_014347.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.133

Variant links:

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]

ZNF324 links:

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ACMG classification

Classification made for transcript

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=0.09201634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF324	NM_014347.3 link	c.467C>A	p.Ala156Asp	missense_variant	Exon 4 of 4	ENST00000196482.4	NP_055162.1	O75467A0A024R4R8
ZNF324	XM_005258713.5 link	c.482C>A	p.Ala161Asp	missense_variant	Exon 4 of 4		XP_005258770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF324	ENST00000196482.4 link	c.467C>A	p.Ala156Asp	missense_variant	Exon 4 of 4	1	NM_014347.3	ENSP00000196482.3	O75467
ZNF324	ENST00000536459.6 link	c.467C>A	p.Ala156Asp	missense_variant	Exon 4 of 4	2		ENSP00000444812.1	O75467
ZNF324	ENST00000593925.1 link	c.41C>A	p.Ala14Asp	missense_variant	Exon 1 of 2	2		ENSP00000471778.1	M0R1C8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251320

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.6

DANN

Benign

0.92

DEOGEN2

Benign

0.023

.;T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.81

T;.;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.092

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

.;L;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.2

.;N;N

REVEL

Benign

0.032

Sift

Benign

0.22

.;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.48

.;P;P

Vest4

0.42

MutPred

0.28

Loss of MoRF binding (P = 0.0375);Loss of MoRF binding (P = 0.0375);Loss of MoRF binding (P = 0.0375);

MVP

0.27

MPC

1.4

ClinPred

0.077

GERP RS

-2.6

Varity_R

0.10

gMVP

0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over