Variant 1-179383513-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144696.6(AXDND1):c.710T>A(p.Val237Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00184 in 1,613,856 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 6 hom. )

Consequence

AXDND1
NM_144696.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

Variant links:

Genes affected

AXDND1 (HGNC:26564): (axonemal dynein light chain domain containing 1)

AXDND1 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=0.008301586).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXDND1	NM_144696.6 link	c.710T>A	p.Val237Glu	missense_variant	Exon 8 of 26	ENST00000367618.8	NP_653297.3	Q5T1B0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXDND1	ENST00000367618.8 link	c.710T>A	p.Val237Glu	missense_variant	Exon 8 of 26	1	NM_144696.6	ENSP00000356590.3		Q5T1B0-1

Frequencies

GnomAD3 genomes

AF:

0.00178

AC:

271

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00158

AC:

397

AN:

251280

Hom.:

AF XY:

0.00172

AC XY:

234

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00883

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00183

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00185

AC:

2697

AN:

1461618

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

1350

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00942

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000441

Gnomad4 FIN exome

AF:

0.000712

Gnomad4 NFE exome

AF:

0.00194

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00178

AC:

271

AN:

152238

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

120

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00213

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00240

Hom.:

Bravo

AF:

0.00190

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00148

AC:

180

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00268

EpiControl

AF:

0.00208

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 21, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.710T>A (p.V237E) alteration is located in exon 8 (coding exon 7) of the AXDND1 gene. This alteration results from a T to A substitution at nucleotide position 710, causing the valine (V) at amino acid position 237 to be replaced by a glutamic acid (E). 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

0.20

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

T;T;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

.;M;.

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.7

.;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0010

.;D;D

Sift4G

Uncertain

0.0030

D;T;T

Polyphen

1.0

.;D;.

Vest4

0.52

MVP

0.40

MPC

0.14

ClinPred

0.024

GERP RS

4.0

Varity_R

0.67

gMVP

0.62

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

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