Variant 6-167902355-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001386888.1(AFDN):c.1619T>C(p.Ile540Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000316 in 1,612,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

AFDN
NM_001386888.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

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]

AFDN links:

AFDN (HGNC:):

AFDN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027314961).

BS2

High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFDN	NM_001386888.1 linkuse as main transcript	c.1619T>C	p.Ile540Thr	missense_variant	12/34	ENST00000683244.1	NP_001373817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFDN	ENST00000683244.1 linkuse as main transcript	c.1619T>C	p.Ile540Thr	missense_variant	12/34		NM_001386888.1	ENSP00000507324.1		A0A804HJ20

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000358

AC:

AN:

251406

Hom.:

AF XY:

0.000353

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000317

AC:

463

AN:

1460776

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

211

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00113

Gnomad4 NFE exome

AF:

0.000333

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000309

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000332

Hom.:

Bravo

AF:

0.000178

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000428

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000119

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

Aug 02, 2021

The c.1571T>C (p.I524T) alteration is located in exon 11 (coding exon 11) of the AFDN gene. This alteration results from a T to C substitution at nucleotide position 1571, causing the isoleucine (I) at amino acid position 524 to be replaced by a threonine (T). 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

0.30

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

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

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.043

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

D;D;D;D;D;D;D

M_CAP

Benign

0.0071

MetaRNN

Benign

0.027

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

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

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

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.8

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

REVEL

Benign

0.059

Sift

Benign

0.032

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

Sift4G

Benign

0.098

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

Polyphen

0.37, 0.13

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

Vest4

0.35

MVP

0.043

MPC

0.60

ClinPred

0.039

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.28

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