Variant 8-81703028-T-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 ENST00000220669.10(ZFAND1):c.577A>C(p.Ile193Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,431,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I193V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZFAND1
ENST00000220669.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15

Variant links:

Genes affected

ZFAND1 (HGNC:25858): (zinc finger AN1-type containing 1) Enables proteasome binding activity. Involved in cellular response to arsenite ion; positive regulation of intracellular protein transport; and stress granule disassembly. Located in cytoplasmic stress granule. [provided by Alliance of Genome Resources, Apr 2022]

ZFAND1 links:

ZFAND1 (HGNC:):

ZFAND1 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=0.09623748).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAND1	NM_024699.3 linkuse as main transcript	c.577A>C	p.Ile193Leu	missense_variant	7/8	ENST00000220669.10	NP_078975.2	Q8TCF1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFAND1	ENST00000220669.10 linkuse as main transcript	c.577A>C	p.Ile193Leu	missense_variant	7/8	1	NM_024699.3	ENSP00000220669.5		Q8TCF1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000415

AC:

AN:

241166

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130610

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:

0.00000914

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1431790

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710192

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:

0.00000274

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

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

Oct 14, 2023

The c.577A>C (p.I193L) alteration is located in exon 7 (coding exon 7) of the ZFAND1 gene. This alteration results from a A to C substitution at nucleotide position 577, causing the isoleucine (I) at amino acid position 193 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.028

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

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

D;D;.;D;D;D;D;D;D

M_CAP

Benign

0.0051

MetaRNN

Benign

0.096

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

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.49

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

MutationTaster

Benign

0.97

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

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.3

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

REVEL

Benign

0.23

Sift

Benign

0.43

T;T;D;D;D;D;T;T;D

Sift4G

Benign

0.20

T;T;D;D;D;.;D;T;D

Polyphen

0.012

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

Vest4

0.44

MutPred

0.58

.;Loss of catalytic residue at I193 (P = 0.0989);.;.;.;.;.;Loss of catalytic residue at I193 (P = 0.0989);.;

MVP

0.10

MPC

0.033

ClinPred

0.16

GERP RS

3.1

Varity_R

0.088

gMVP

0.28

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