14-50587817-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015915.5(ATL1):​c.35-14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,614,164 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 15 hom., cov: 32)
Exomes 𝑓: 0.00079 ( 11 hom. )

Consequence

ATL1
NM_015915.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.975
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 14-50587817-G-A is Benign according to our data. Variant chr14-50587817-G-A is described in ClinVar as [Benign]. Clinvar id is 516491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00834 (1271/152332) while in subpopulation AFR AF= 0.0287 (1192/41580). AF 95% confidence interval is 0.0273. There are 15 homozygotes in gnomad4. There are 617 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 15 SD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATL1NM_015915.5 linkc.35-14G>A intron_variant Intron 1 of 13 ENST00000358385.12 NP_056999.2 Q8WXF7-1A0A0S2Z5B0Q53F53
ATL1NM_001127713.1 linkc.35-14G>A intron_variant Intron 2 of 13 NP_001121185.1 Q8WXF7-2A0A0S2Z5A2Q53F53
ATL1NM_181598.4 linkc.35-14G>A intron_variant Intron 1 of 12 NP_853629.2 Q8WXF7-2A0A0S2Z5A2Q53F53
ATL1XM_047431430.1 linkc.35-14G>A intron_variant Intron 2 of 14 XP_047287386.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATL1ENST00000358385.12 linkc.35-14G>A intron_variant Intron 1 of 13 1 NM_015915.5 ENSP00000351155.7 Q8WXF7-1

Frequencies

GnomAD3 genomes
AF:
0.00834
AC:
1269
AN:
152214
Hom.:
15
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0287
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00334
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:
0.000103
Gnomad OTH
AF:
0.0100
GnomAD3 exomes
AF:
0.00219
AC:
550
AN:
251250
Hom.:
6
AF XY:
0.00152
AC XY:
207
AN XY:
135828
show subpopulations
Gnomad AFR exome
AF:
0.0291
Gnomad AMR exome
AF:
0.00173
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:
0.0000440
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.000788
AC:
1152
AN:
1461832
Hom.:
11
Cov.:
31
AF XY:
0.000624
AC XY:
454
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.0276
Gnomad4 AMR exome
AF:
0.00154
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000378
Gnomad4 OTH exome
AF:
0.00179
GnomAD4 genome
AF:
0.00834
AC:
1271
AN:
152332
Hom.:
15
Cov.:
32
AF XY:
0.00828
AC XY:
617
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0287
Gnomad4 AMR
AF:
0.00334
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00993
Alfa
AF:
0.00305
Hom.:
0
Bravo
AF:
0.00947
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 3A Benign:2
Jan 17, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Dec 05, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:2
Oct 15, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

not specified Benign:1
Aug 07, 2017
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Neuropathy, hereditary sensory, type 1D Benign:1
Dec 05, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.63
DANN
Benign
0.48

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.

Other links and lift over

dbSNP: rs115722924; hg19: chr14-51054535; API