Variant 15-80121796-C-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_019006.4(ZFAND6):c.239C>G(p.Ser80Cys) 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 1,461,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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

ZFAND6
NM_019006.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

Variant links:

Genes affected

ZFAND6 (HGNC:30164): (zinc finger AN1-type containing 6) Predicted to enable polyubiquitin modification-dependent protein binding activity. Involved in cellular response to tumor necrosis factor; negative regulation of apoptotic process; and regulation of I-kappaB kinase/NF-kappaB signaling. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ZFAND6 links:

ZFAND6 (HGNC:):

ZFAND6 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=0.20306233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAND6	NM_019006.4 linkuse as main transcript	c.239C>G	p.Ser80Cys	missense_variant	4/7	ENST00000261749.11	NP_061879.2	Q6FIF0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFAND6	ENST00000261749.11 linkuse as main transcript	c.239C>G	p.Ser80Cys	missense_variant	4/7	1	NM_019006.4	ENSP00000261749.6		Q6FIF0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250962

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135654

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461398

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727008

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

May 15, 2024

The c.239C>G (p.S80C) alteration is located in exon 4 (coding exon 2) of the ZFAND6 gene. This alteration results from a C to G substitution at nucleotide position 239, causing the serine (S) at amino acid position 80 to be replaced by a cysteine (C). 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

0.077

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.23

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

Eigen

Benign

0.13

Eigen_PC

Benign

0.093

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

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

M_CAP

Benign

0.0068

MetaRNN

Benign

0.20

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

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.2

M;M;M;.;.;M;M;M;M;.;.;.;.;.;M;M;.

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.8

.;D;D;D;D;D;.;D;D;D;N;D;D;D;D;.;D

REVEL

Benign

0.087

Sift

Benign

0.075

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

Sift4G

Benign

0.071

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

Polyphen

0.88

P;P;P;D;.;P;P;P;P;.;.;.;.;.;P;P;.

Vest4

0.28

MutPred

0.17

Loss of phosphorylation at S80 (P = 0.0137);Loss of phosphorylation at S80 (P = 0.0137);Loss of phosphorylation at S80 (P = 0.0137);.;Loss of phosphorylation at S80 (P = 0.0137);Loss of phosphorylation at S80 (P = 0.0137);Loss of phosphorylation at S80 (P = 0.0137);Loss of phosphorylation at S80 (P = 0.0137);Loss of phosphorylation at S80 (P = 0.0137);Loss of phosphorylation at S80 (P = 0.0137);Loss of phosphorylation at S80 (P = 0.0137);.;.;Loss of phosphorylation at S80 (P = 0.0137);Loss of phosphorylation at S80 (P = 0.0137);Loss of phosphorylation at S80 (P = 0.0137);.;

MVP

0.048

MPC

1.0

ClinPred

0.58

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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