Variant 15-80121810-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_019006.4(ZFAND6):c.253A>G(p.Met85Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000887 in 1,612,910 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 (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

ZFAND6
NM_019006.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.386

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:

Genome browser will be placed here

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=0.006631404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAND6	NM_019006.4 linkuse as main transcript	c.253A>G	p.Met85Val	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.253A>G	p.Met85Val	missense_variant	4/7	1	NM_019006.4	ENSP00000261749.6		Q6FIF0-1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000168

AC:

AN:

250608

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

135440

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000795

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000897

AC:

131

AN:

1460602

Hom.:

Cov.:

AF XY:

0.0000950

AC XY:

AN XY:

726648

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00195

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000293

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000148

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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 21, 2023

The c.253A>G (p.M85V) alteration is located in exon 4 (coding exon 2) of the ZFAND6 gene. This alteration results from a A to G substitution at nucleotide position 253, causing the methionine (M) at amino acid position 85 to be replaced by a valine (V). 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

0.053

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.0040

DANN

Benign

0.44

DEOGEN2

Benign

0.023

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

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.19

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

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0066

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.060

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

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.97

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

REVEL

Benign

0.053

Sift

Benign

0.60

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

Sift4G

Benign

0.40

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

Polyphen

0.0

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

Vest4

0.19

MVP

0.014

MPC

0.62

ClinPred

0.0037

GERP RS

-8.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.039

gMVP

0.46

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