Variant 15-80122784-A-C 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.348A>C(p.Glu116Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,612,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

ZFAND6
NM_019006.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

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:

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=0.08175054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAND6	NM_019006.4 linkuse as main transcript	c.348A>C	p.Glu116Asp	missense_variant	5/7	ENST00000261749.11	NP_061879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFAND6	ENST00000261749.11 linkuse as main transcript	c.348A>C	p.Glu116Asp	missense_variant	5/7	1	NM_019006.4	ENSP00000261749	P1	Q6FIF0-1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152208

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250998

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135672

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000548

AC:

AN:

1460456

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

726654

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:

0.0000702

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74368

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 09, 2023

The c.348A>C (p.E116D) alteration is located in exon 5 (coding exon 3) of the ZFAND6 gene. This alteration results from a A to C substitution at nucleotide position 348, causing the glutamic acid (E) at amino acid position 116 to be replaced by an aspartic acid (D). 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

0.081

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

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

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.73

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

M_CAP

Benign

0.0029

MetaRNN

Benign

0.082

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

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

L;L;L;.;.;L;L;L;L;.;.;.;.;L;L;.

MutationTaster

Benign

0.60

D;D;D;D;D;D;D;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.1

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

REVEL

Benign

0.11

Sift

Benign

0.32

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

Sift4G

Benign

0.41

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

Polyphen

0.0020

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

Vest4

0.26

MutPred

0.18

Gain of glycosylation at T117 (P = 0.0899);Gain of glycosylation at T117 (P = 0.0899);Gain of glycosylation at T117 (P = 0.0899);.;Gain of glycosylation at T117 (P = 0.0899);Gain of glycosylation at T117 (P = 0.0899);Gain of glycosylation at T117 (P = 0.0899);Gain of glycosylation at T117 (P = 0.0899);Gain of glycosylation at T117 (P = 0.0899);Gain of glycosylation at T117 (P = 0.0899);.;.;Gain of glycosylation at T117 (P = 0.0899);Gain of glycosylation at T117 (P = 0.0899);Gain of glycosylation at T117 (P = 0.0899);.;

MVP

0.055

MPC

0.55

ClinPred

0.051

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.043

gMVP

0.41

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