6-167911425-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001386888.1(AFDN):ā€‹c.1973A>Gā€‹(p.Glu658Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00018 ( 0 hom., cov: 33)
Exomes š‘“: 0.00018 ( 0 hom. )

Consequence

AFDN
NM_001386888.1 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.76
Variant links:
Genes affected
AFDN (HGNC:7137): (afadin, adherens junction formation factor) This gene encodes a multi-domain protein involved in signaling and organization of cell junctions during embryogenesis. It has also been identified as the fusion partner of acute lymphoblastic leukemia (ALL-1) gene, involved in acute myeloid leukemias with t(6;11)(q27;q23) translocation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, however, not all have been fully characterized.[provided by RefSeq, May 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.15937719).
BS2
High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AFDNNM_001386888.1 linkc.1973A>G p.Glu658Gly missense_variant 15/34 ENST00000683244.1 NP_001373817.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AFDNENST00000683244.1 linkc.1973A>G p.Glu658Gly missense_variant 15/34 NM_001386888.1 ENSP00000507324.1 A0A804HJ20

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152076
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000416
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000271
AC:
68
AN:
251378
Hom.:
0
AF XY:
0.000316
AC XY:
43
AN XY:
135864
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00357
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000555
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000792
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000184
AC:
269
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.000208
AC XY:
151
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00494
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000441
Gnomad4 OTH exome
AF:
0.000497
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152076
Hom.:
0
Cov.:
33
AF XY:
0.000202
AC XY:
15
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000416
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000473
Hom.:
0
Bravo
AF:
0.000166
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000280
AC:
34
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000237

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 submitterclinical testingAmbry GeneticsAug 12, 2021The c.1925A>G (p.E642G) alteration is located in exon 14 (coding exon 14) of the AFDN gene. This alteration results from a A to G substitution at nucleotide position 1925, causing the glutamic acid (E) at amino acid position 642 to be replaced by a glycine (G). 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
Uncertain
0.37
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.20
T;T;.;.;D;.;T
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D;D
M_CAP
Uncertain
0.091
D
MetaRNN
Benign
0.16
T;T;T;T;T;T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.3
.;.;M;.;M;.;.
PrimateAI
Benign
0.48
T
PROVEAN
Pathogenic
-6.0
D;D;D;D;D;D;.
REVEL
Uncertain
0.50
Sift
Uncertain
0.018
D;D;D;D;D;D;.
Sift4G
Uncertain
0.0030
D;D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;.;D;.
Vest4
0.83
MVP
0.39
MPC
1.2
ClinPred
0.21
T
GERP RS
5.5
Varity_R
0.53
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs148916042; hg19: chr6-168312105; API