rs200747906

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015459.5(ATL3):​c.712-8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,602,972 control chromosomes in the GnomAD database, including 3 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00051 ( 3 hom. )

Consequence

ATL3
NM_015459.5 splice_region, intron

Scores

2
Splicing: ADA: 0.00001826
2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.65
Variant links:
Genes affected
ATL3 (HGNC:24526): (atlastin GTPase 3) This gene encodes a member of a family of dynamin-like, integral membrane GTPases. The encoded protein is required for the proper formation of the network of interconnected tubules of the endoplasmic reticulum. Mutations in this gene may be associated with hereditary sensory neuropathy type IF. Alternatively spliced transcript variants that encode distinct isoforms have been described. [provided by RefSeq, Feb 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.03).
BP6
Variant 11-63643503-T-C is Benign according to our data. Variant chr11-63643503-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 541689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 69 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATL3NM_015459.5 linkc.712-8A>G splice_region_variant, intron_variant Intron 7 of 12 ENST00000398868.8 NP_056274.3 Q6DD88
ATL3NM_001290048.2 linkc.658-8A>G splice_region_variant, intron_variant Intron 7 of 12 NP_001276977.1 Q6DD88F5H6I7B4DXC4
ATL3XM_047426725.1 linkc.868-8A>G splice_region_variant, intron_variant Intron 8 of 13 XP_047282681.1
ATL3XM_006718493.2 linkc.655-8A>G splice_region_variant, intron_variant Intron 6 of 11 XP_006718556.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATL3ENST00000398868.8 linkc.712-8A>G splice_region_variant, intron_variant Intron 7 of 12 1 NM_015459.5 ENSP00000381844.3 Q6DD88
ATL3ENST00000538786.1 linkc.658-8A>G splice_region_variant, intron_variant Intron 7 of 12 2 ENSP00000437593.1 F5H6I7
ENSG00000256789ENST00000540307.1 linkn.59+5768T>C intron_variant Intron 1 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.000453
AC:
69
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000524
Gnomad ASJ
AF:
0.00950
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000689
AC:
165
AN:
239368
Hom.:
1
AF XY:
0.000623
AC XY:
81
AN XY:
130108
show subpopulations
Gnomad AFR exome
AF:
0.000132
Gnomad AMR exome
AF:
0.000470
Gnomad ASJ exome
AF:
0.0109
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000246
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000274
Gnomad OTH exome
AF:
0.000869
GnomAD4 exome
AF:
0.000508
AC:
737
AN:
1450688
Hom.:
3
Cov.:
30
AF XY:
0.000488
AC XY:
352
AN XY:
721024
show subpopulations
Gnomad4 AFR exome
AF:
0.0000604
Gnomad4 AMR exome
AF:
0.000394
Gnomad4 ASJ exome
AF:
0.0103
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.000167
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000351
Gnomad4 OTH exome
AF:
0.000750
GnomAD4 genome
AF:
0.000453
AC:
69
AN:
152284
Hom.:
0
Cov.:
32
AF XY:
0.000456
AC XY:
34
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00950
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.00117
Hom.:
0
Bravo
AF:
0.000480

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Neuropathy, hereditary sensory, type 1F Benign:2
Dec 05, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jan 11, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:2
May 26, 2021
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.57
DANN
Benign
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000018
dbscSNV1_RF
Benign
0.0040
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: rs200747906; hg19: chr11-63410975; API