NM_015459.5:c.978+9G>A

Variant names:

• chr11-63636198-C-T
• rs3781606
• NM_015459.5:c.978+9G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015459.5(ATL3):​c.978+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,608,698 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00029 (4 hom.)
• Consequence: ATL3 NM_015459.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.00500
• Publications: 2 publications found

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]

ATL3 Gene-Disease associations (from GenCC):

• neuropathy, hereditary sensory, type 1F

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• hereditary sensory and autonomic neuropathy type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000256789 (HGNC:58146):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-63636198-C-T is Benign according to our data. Variant chr11-63636198-C-T is described in ClinVar as Benign. ClinVar VariationId is 474842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 37 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015459.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATL3	NM_015459.5	MANE Select	c.978+9G>A		intron	N/A	NP_056274.3
	ATL3	NM_001440716.1		c.927+9G>A		intron	N/A	NP_001427645.1
	ATL3	NM_001290048.2		c.924+9G>A		intron	N/A	NP_001276977.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATL3	ENST00000398868.8	TSL:1 MANE Select	c.978+9G>A		intron	N/A	ENSP00000381844.3
	ATL3	ENST00000538786.1	TSL:2	c.924+9G>A		intron	N/A	ENSP00000437593.1
	ENSG00000256789	ENST00000540307.2	TSL:3	n.121-1293C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000244 AC: 37 AN: 151806 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00695

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000699 AC: 171 AN: 244680 AF XY: 0.000543

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00926

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.000336

GnomAD4 exome AF: 0.000288 AC: 420 AN: 1456774 Hom.: 4 Cov.: 31 AF XY: 0.000283 AC XY: 205 AN XY: 724570

African (AFR) AF: 0.00 AC: 0 AN: 33260

American (AMR) AF: 0.0000230 AC: 1 AN: 43406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25930

East Asian (EAS) AF: 0.00948 AC: 376 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1110110

Other (OTH) AF: 0.000615 AC: 37 AN: 60204

GnomAD4 genome AF: 0.000244 AC: 37 AN: 151924 Hom.: 0 Cov.: 30 AF XY: 0.000242 AC XY: 18 AN XY: 74262

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.0000656 AC: 1 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00696 AC: 36 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67928

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.0000481 Hom.: 0

Bravo AF: 0.000264

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Neuropathy, hereditary sensory, type 1F Benign:1

Dec 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ATL3-related disorder Benign:1

Mar 27, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		-0.0050
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3781606; hg19: chr11-63403670;