Variant 1-179395121-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144696.6(AXDND1):c.1028A>G(p.His343Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000905 in 1,613,150 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 (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

AXDND1
NM_144696.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.69

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.067677885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXDND1	NM_144696.6 linkuse as main transcript	c.1028A>G	p.His343Arg	missense_variant	11/26	ENST00000367618.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXDND1	ENST00000367618.8 linkuse as main transcript	c.1028A>G	p.His343Arg	missense_variant	11/26	1	NM_144696.6	P2	Q5T1B0-1

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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

GnomAD3 exomes

AF:

0.000139

AC:

AN:

250930

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.000349

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000541

AC:

AN:

1460782

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.00162

Gnomad4 AMR exome

AF:

0.000336

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:

0.000149

GnomAD4 genome

AF:

0.000440

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.000392

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:

0.000473

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000529

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000198

AC:

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 12, 2023

The c.1028A>G (p.H343R) alteration is located in exon 11 (coding exon 10) of the AXDND1 gene. This alteration results from a A to G substitution at nucleotide position 1028, causing the histidine (H) at amino acid position 343 to be replaced by an arginine (R). 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

0.15

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.26

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.25

T;T;.

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-0.46

MutationTaster

Benign

0.88

D;D

PrimateAI

Uncertain

0.65

Sift4G

Uncertain

0.015

D;D;T

Polyphen

0.98

.;D;.

Vest4

0.58

MVP

0.61

MPC

0.16

ClinPred

0.13

GERP RS

5.7

Varity_R

0.66

gMVP

0.54

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