dbSNP rs199947499: AXDND1:p.Arg152His (chr1-179378717-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_144696.6(AXDND1):c.455G>A(p.Arg152His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,588,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R152C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

AXDND1
NM_144696.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.69

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014499754).

BP6

Variant 1-179378717-G-A is Benign according to our data. Variant chr1-179378717-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2544188.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144696.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXDND1	NM_144696.6	MANE Select	c.455G>A	p.Arg152His	missense	Exon 5 of 26	NP_653297.3
	AXDND1	NR_073544.2		n.644G>A		non_coding_transcript_exon	Exon 5 of 26

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AXDND1	ENST00000367618.8	TSL:1 MANE Select	c.455G>A	p.Arg152His	missense	Exon 5 of 26	ENSP00000356590.3	Q5T1B0-1
AXDND1	ENST00000434088.1	TSL:1	c.257G>A	p.Arg86His	missense	Exon 3 of 22	ENSP00000391716.1	B1AM31
AXDND1	ENST00000511157.5	TSL:1	n.455G>A		non_coding_transcript_exon	Exon 5 of 26	ENSP00000424373.1	A6H900

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000901

AC:

AN:

244212

AF XY:

0.0000908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000305

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00100

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000359

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000209

AC:

AN:

1436180

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

713710

show subpopulations

African (AFR)

AF:

0.0000604

AC:

AN:

33124

American (AMR)

AF:

0.0000230

AC:

AN:

43416

Ashkenazi Jewish (ASJ)

AF:

0.0000391

AC:

AN:

25596

East Asian (EAS)

AF:

0.000443

AC:

AN:

38384

South Asian (SAS)

AF:

0.0000247

AC:

AN:

80840

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.00000456

AC:

AN:

1097594

Other (OTH)

AF:

0.0000338

AC:

AN:

59116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41522

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.0070

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.025

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.65

M_CAP

Benign

0.0033

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

-1.7

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.010

Sift

Benign

0.087

Sift4G

Benign

0.64

Polyphen

0.0060

Vest4

0.022

MVP

0.048

MPC

0.029

ClinPred

0.026

GERP RS

-3.7

Varity_R

0.026

gMVP

0.17

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over