Variant chr15-80131266-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019006.4(ZFAND6):c.451A>T(p.Met151Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,216 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZFAND6
NM_019006.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAND6	NM_019006.4 linkuse as main transcript	c.451A>T	p.Met151Leu	missense_variant	6/7	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.451A>T	p.Met151Leu	missense_variant	6/7	1	NM_019006.4	ENSP00000261749.6		Q6FIF0-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460996

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726828

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

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:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.00000756

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

Jun 07, 2023

The c.451A>T (p.M151L) alteration is located in exon 6 (coding exon 4) of the ZFAND6 gene. This alteration results from a A to T substitution at nucleotide position 451, causing the methionine (M) at amino acid position 151 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

0.23

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.037

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

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

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

M_CAP

Benign

0.0078

MetaRNN

Uncertain

0.48

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

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

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.5

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

REVEL

Benign

0.11

Sift

Benign

0.045

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

Sift4G

Benign

0.11

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

Polyphen

0.70

P;P;P;B;P;P;P;P;.;.;P;P;.

Vest4

0.30

MutPred

0.37

Loss of MoRF binding (P = 0.1072);Loss of MoRF binding (P = 0.1072);Loss of MoRF binding (P = 0.1072);.;Loss of MoRF binding (P = 0.1072);Loss of MoRF binding (P = 0.1072);Loss of MoRF binding (P = 0.1072);Loss of MoRF binding (P = 0.1072);Loss of MoRF binding (P = 0.1072);Loss of MoRF binding (P = 0.1072);Loss of MoRF binding (P = 0.1072);Loss of MoRF binding (P = 0.1072);.;

MVP

0.15

MPC

1.0

ClinPred

0.88

GERP RS

5.3

Varity_R

0.19

gMVP

0.64

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