Variant 6-38061767-A-G 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_021943.3(ZFAND3):c.287A>G(p.Lys96Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,156 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ZFAND3
NM_021943.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

Variant links:

Genes affected

ZFAND3 (HGNC:18019): (zinc finger AN1-type containing 3) Predicted to enable DNA binding activity and zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZFAND3 links:

Genome browser will be placed here

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=0.08604926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZFAND3	NM_021943.3 linkuse as main transcript	c.287A>G	p.Lys96Arg	missense_variant	3/6	ENST00000287218.9
ZFAND3	NM_001410904.1 linkuse as main transcript	c.287A>G	p.Lys96Arg	missense_variant	3/5
ZFAND3	XM_017011171.3 linkuse as main transcript	c.239A>G	p.Lys80Arg	missense_variant	2/5
ZFAND3	XM_011514790.3 linkuse as main transcript	c.287A>G	p.Lys96Arg	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFAND3	ENST00000287218.9 linkuse as main transcript	c.287A>G	p.Lys96Arg	missense_variant	3/6	1	NM_021943.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

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

Dec 22, 2023

The c.287A>G (p.K96R) alteration is located in exon 3 (coding exon 3) of the ZFAND3 gene. This alteration results from a A to G substitution at nucleotide position 287, causing the lysine (K) at amino acid position 96 to be replaced by an arginine (R). 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

0.075

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

T;.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.82

T;T;D

M_CAP

Benign

0.0057

MetaRNN

Benign

0.086

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.;.

MutationTaster

Benign

0.57

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.49

N;N;N

REVEL

Benign

0.062

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.53

T;T;T

Polyphen

0.0030

B;.;.

Vest4

0.46

MutPred

0.29

Loss of ubiquitination at K96 (P = 0.003);Loss of ubiquitination at K96 (P = 0.003);.;

MVP

0.16

MPC

0.20

ClinPred

0.13

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over