Variant 7-1157721-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000316495.8(ZFAND2A):c.85A>G(p.Lys29Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000568 in 1,409,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

ZFAND2A
ENST00000316495.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.794

Variant links:

Genes affected

ZFAND2A (HGNC:28073): (zinc finger AN1-type containing 2A) Predicted to enable zinc ion binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process and protein targeting to ER. Predicted to act upstream of or within cellular response to arsenic-containing substance and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Predicted to be located in nucleus. Predicted to be part of proteasome complex. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZFAND2A links:

ZFAND2A (HGNC:):

ZFAND2A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05079496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAND2A	NM_182491.4 linkuse as main transcript	c.85A>G	p.Lys29Glu	missense_variant	3/5	ENST00000316495.8	NP_872297.2	Q8N6M9
ZFAND2A	NM_001365383.1 linkuse as main transcript	c.85A>G	p.Lys29Glu	missense_variant	3/6		NP_001352312.1
ZFAND2A	NM_001365381.2 linkuse as main transcript	c.85A>G	p.Lys29Glu	missense_variant	3/5		NP_001352310.1
ZFAND2A	NR_158186.2 linkuse as main transcript	n.363A>G		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFAND2A	ENST00000316495.8 linkuse as main transcript	c.85A>G	p.Lys29Glu	missense_variant	3/5	1	NM_182491.4	ENSP00000314619.3		Q8N6M9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000568

AC:

AN:

1409510

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

697094

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:

0.00000734

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 06, 2021

The c.85A>G (p.K29E) alteration is located in exon 3 (coding exon 2) of the ZFAND2A gene. This alteration results from a A to G substitution at nucleotide position 85, causing the lysine (K) at amino acid position 29 to be replaced by a glutamic acid (E). 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

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.0080

T;.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.48

T;T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.051

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.15

.;.;N

MutationTaster

Benign

0.93

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.60

N;N;N

REVEL

Benign

0.027

Sift

Benign

0.97

T;T;T

Sift4G

Benign

0.77

T;.;T

Polyphen

0.025, 0.0

.;B;B

Vest4

0.13

MutPred

0.37

Loss of methylation at K29 (P = 7e-04);Loss of methylation at K29 (P = 7e-04);Loss of methylation at K29 (P = 7e-04);

MVP

0.11

MPC

0.0083

ClinPred

0.10

GERP RS

0.22

Varity_R

0.14

gMVP

0.10

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