Variant 19-57211402-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003417.5(ZNF264):c.305C>A(p.Ala102Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF264
NM_003417.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.475

Variant links:

Genes affected

ZNF264 (HGNC:13057): (zinc finger protein 264) This gene encodes a zinc finger protein and belongs to the krueppel C2H2-type zinc-finger protein family. Zinc finger proteins are often localized in the nucleus, bind nucleic acids, and regulate transcription. [provided by RefSeq, Jan 2010]

ZNF264 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=0.105778664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF264	NM_003417.5 linkuse as main transcript	c.305C>A	p.Ala102Asp	missense_variant	4/4	ENST00000263095.10	NP_003408.1	O43296
ZNF264	XM_047439724.1 linkuse as main transcript	c.305C>A	p.Ala102Asp	missense_variant	5/5		XP_047295680.1
ZNF264	XM_011527522.3 linkuse as main transcript	c.209C>A	p.Ala70Asp	missense_variant	3/3		XP_011525824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF264	ENST00000263095.10 linkuse as main transcript	c.305C>A	p.Ala102Asp	missense_variant	4/4	2	NM_003417.5	ENSP00000263095.5		O43296
ZNF264	ENST00000597447.5 linkuse as main transcript	c.209C>A	p.Ala70Asp	missense_variant	3/3	3		ENSP00000470587.1		M0QZJ4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461736

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727160

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.305C>A (p.A102D) alteration is located in exon 4 (coding exon 4) of the ZNF264 gene. This alteration results from a C to A substitution at nucleotide position 305, causing the alanine (A) at amino acid position 102 to be replaced by an aspartic acid (D). 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

0.098

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.26

DEOGEN2

Benign

0.027

T;T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.012

.;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-2.7

D;.;D

REVEL

Benign

0.056

Sift

Benign

0.38

T;.;T

Sift4G

Benign

0.66

T;D;T

Polyphen

0.62

P;.;P

Vest4

0.14

MutPred

0.17

Gain of phosphorylation at S104 (P = 0.1458);.;Gain of phosphorylation at S104 (P = 0.1458);

MVP

0.13

MPC

0.089

ClinPred

0.33

GERP RS

0.21

Varity_R

0.17

gMVP

0.073

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over