Genetic Variant ZFAND2B:p.Gln91Arg (chr2-219207769-A-G) – 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_138802.3(ZFAND2B):c.272A>G(p.Gln91Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,614,056 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZFAND2B
NM_138802.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16

Variant links:

Genes affected

ZFAND2B (HGNC:25206): (zinc finger AN1-type containing 2B) This gene encodes a protein containing AN1-type zinc-fingers and ubiquitin-interacting motifs. The encoded protein likely associates with the proteosome to stimulate the degradation of toxic or misfolded proteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

ZFAND2B 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=0.09420404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAND2B	NM_138802.3 link	c.272A>G	p.Gln91Arg	missense_variant	Exon 3 of 9	ENST00000289528.10	NP_620157.1	Q8WV99-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAND2B	ENST00000289528.10 link	c.272A>G	p.Gln91Arg	missense_variant	Exon 3 of 9	1	NM_138802.3	ENSP00000289528.5		Q8WV99-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251352

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.272A>G (p.Q91R) alteration is located in exon 3 (coding exon 3) of the ZFAND2B gene. This alteration results from a A to G substitution at nucleotide position 272, causing the glutamine (Q) at amino acid position 91 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

0.090

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0049

.;T;.;T;T;T;T;T;T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.038

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.77

.;T;T;.;T;.;T;.;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.094

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.39

N;N;N;N;.;.;.;N;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.47

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.081

Sift

Benign

0.36

T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.44

T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

.;B;.;B;.;.;B;B;.;.

Vest4

0.17

MutPred

0.20

Gain of MoRF binding (P = 0.0416);Gain of MoRF binding (P = 0.0416);Gain of MoRF binding (P = 0.0416);Gain of MoRF binding (P = 0.0416);Gain of MoRF binding (P = 0.0416);Gain of MoRF binding (P = 0.0416);Gain of MoRF binding (P = 0.0416);Gain of MoRF binding (P = 0.0416);Gain of MoRF binding (P = 0.0416);Gain of MoRF binding (P = 0.0416);

MVP

0.33

MPC

0.13

ClinPred

0.18

GERP RS

4.0

Varity_R

0.12

gMVP

0.29

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over