Variant 15-80121729-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.172C>G(p.Leu58Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 6.8e-7 ( 0 hom. )

Consequence

ZFAND6
NM_019006.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

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:

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=0.094688386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAND6	NM_019006.4 linkuse as main transcript	c.172C>G	p.Leu58Val	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.172C>G	p.Leu58Val	missense_variant	4/7	1	NM_019006.4	ENSP00000261749.6		Q6FIF0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461490

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727056

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 19, 2023

The c.172C>G (p.L58V) 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 172, causing the leucine (L) at amino acid position 58 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

0.060

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0066

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

Eigen

Benign

-0.21

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.74

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

M_CAP

Benign

0.0047

MetaRNN

Benign

0.095

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

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

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.010

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

REVEL

Benign

0.090

Sift

Benign

0.26

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

Sift4G

Benign

0.35

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

Polyphen

0.015

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

Vest4

0.14

MutPred

0.14

Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);.;Loss of solvent accessibility (P = 0.0155);.;Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);.;

MVP

0.040

MPC

0.63

ClinPred

0.31

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.56

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over