chr14-50595639-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015915.5(ATL1):c.630+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,612,016 control chromosomes in the GnomAD database, including 16,779 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2587 hom., cov: 31)

Exomes 𝑓: 0.13 ( 14192 hom. )

Consequence

ATL1
NM_015915.5 splice_region, intron

Scores

Splicing: ADA: 0.00008445

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.130

Publications

7 publications found

Variant links:

Genes affected

ATL1 (HGNC:11231): (atlastin GTPase 1) The protein encoded by this gene is a GTPase and a Golgi body transmembrane protein. The encoded protein can form a homotetramer and has been shown to interact with spastin and with mitogen-activated protein kinase kinase kinase kinase 4. This protein may be involved in axonal maintenance as evidenced by the fact that defects in this gene are a cause of spastic paraplegia type 3. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ATL1 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 3A
Inheritance: AD, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
neuropathy, hereditary sensory, type 1D
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
hereditary sensory and autonomic neuropathy type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ATL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 14-50595639-G-A is Benign according to our data. Variant chr14-50595639-G-A is described in ClinVar as Benign. ClinVar VariationId is 136428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015915.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATL1	NM_015915.5	MANE Select	c.630+7G>A	splice_region intron	N/A	NP_056999.2
ATL1	NM_001127713.1		c.630+7G>A	splice_region intron	N/A	NP_001121185.1	Q53F53
ATL1	NM_181598.4		c.630+7G>A	splice_region intron	N/A	NP_853629.2	Q8WXF7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATL1	ENST00000358385.12	TSL:1 MANE Select	c.630+7G>A	splice_region intron	N/A	ENSP00000351155.7	Q8WXF7-1
ATL1	ENST00000441560.6	TSL:1	c.630+7G>A	splice_region intron	N/A	ENSP00000413675.2	Q8WXF7-2
ATL1	ENST00000682037.1		c.630+7G>A	splice_region intron	N/A	ENSP00000508289.1	A0A804HLC1

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25933

AN:

151834

Hom.:

2588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.0765

Gnomad SAS

AF:

0.0775

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.165

GnomAD2 exomes

AF:

0.129

AC:

32517

AN:

251246

AF XY:

0.125

show subpopulations

Gnomad AFR exome

AF:

0.275

Gnomad AMR exome

AF:

0.0885

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.0735

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.135

AC:

196655

AN:

1460064

Hom.:

14192

Cov.:

AF XY:

0.132

AC XY:

96141

AN XY:

726470

show subpopulations

African (AFR)

AF:

0.281

AC:

9405

AN:

33414

American (AMR)

AF:

0.0919

AC:

4108

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

5468

AN:

26118

East Asian (EAS)

AF:

0.0733

AC:

2909

AN:

39660

South Asian (SAS)

AF:

0.0764

AC:

6585

AN:

86222

European-Finnish (FIN)

AF:

0.131

AC:

6970

AN:

53354

Middle Eastern (MID)

AF:

0.183

AC:

1053

AN:

5760

European-Non Finnish (NFE)

AF:

0.137

AC:

151633

AN:

1110476

Other (OTH)

AF:

0.141

AC:

8524

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

7812

15624

23435

31247

39059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5496

10992

16488

21984

27480

<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:

0.171

AC:

25951

AN:

151952

Hom.:

2587

Cov.:

AF XY:

0.168

AC XY:

12491

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.276

AC:

11443

AN:

41402

American (AMR)

AF:

0.124

AC:

1896

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

736

AN:

3462

East Asian (EAS)

AF:

0.0767

AC:

397

AN:

5178

South Asian (SAS)

AF:

0.0781

AC:

376

AN:

4812

European-Finnish (FIN)

AF:

0.136

AC:

1436

AN:

10552

Middle Eastern (MID)

AF:

0.226

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.134

AC:

9129

AN:

67972

Other (OTH)

AF:

0.162

AC:

342

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1032

2064

3097

4129

5161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<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:

0.155

Hom.:

1224

Bravo

AF:

0.174

Asia WGS

AF:

0.0960

AC:

335

AN:

3478

EpiCase

AF:

0.138

EpiControl

AF:

0.138

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Hereditary spastic paraplegia 3A (3)

ATL1-related disorder (1)

Neuropathy, hereditary sensory, type 1D (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.8

(source)

DANN

Benign

0.51

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000084

dbscSNV1_RF

Benign

0.0

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

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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