rs200026815

Variant names:

• chr11-63631058-G-A
• rs200026815
• NM_015459.5:c.1521C>T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_015459.5(ATL3):​c.1521C>T​(p.Ala507Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,612,034 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00080 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (5 hom.)
• Consequence: ATL3 NM_015459.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.07

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 11-63631058-G-A is Benign according to our data. Variant chr11-63631058-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.07 with no splicing effect.
• BS2: High AC in GnomAd4 at 122 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATL3	NM_015459.5	c.1521C>T	p.Ala507Ala	synonymous_variant	Exon 12 of 13	ENST00000398868.8	NP_056274.3
ATL3	NM_001290048.2	c.1467C>T	p.Ala489Ala	synonymous_variant	Exon 12 of 13		NP_001276977.1
ATL3	XM_047426725.1	c.1677C>T	p.Ala559Ala	synonymous_variant	Exon 13 of 14		XP_047282681.1
ATL3	XM_006718493.2	c.1464C>T	p.Ala488Ala	synonymous_variant	Exon 11 of 12		XP_006718556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATL3	ENST00000398868.8	c.1521C>T	p.Ala507Ala	synonymous_variant	Exon 12 of 13	1	NM_015459.5	ENSP00000381844.3
ATL3	ENST00000538786.1	c.1467C>T	p.Ala489Ala	synonymous_variant	Exon 12 of 13	2		ENSP00000437593.1

Frequencies

GnomAD3 genomes AF: 0.000803 AC: 122 AN: 151944 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000622 AC: 154 AN: 247620 Hom.: 0 AF XY: 0.000648 AC XY: 87 AN XY: 134272

Gnomad AFR exome AF: 0.000582

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000724

Gnomad SAS exome AF: 0.000528

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.000874

Gnomad OTH exome AF: 0.000831

GnomAD4 exome AF: 0.00120 AC: 1753 AN: 1459972 Hom.: 5 Cov.: 32 AF XY: 0.00116 AC XY: 845 AN XY: 726186

Gnomad4 AFR exome AF: 0.000419

Gnomad4 AMR exome AF: 0.000247

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.000640

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.00142

Gnomad4 OTH exome AF: 0.00124

GnomAD4 genome AF: 0.000802 AC: 122 AN: 152062 Hom.: 0 Cov.: 32 AF XY: 0.000794 AC XY: 59 AN XY: 74352

Gnomad4 AFR AF: 0.000362

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00135

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.000839

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ATL3: BP4, BP7 -

Neuropathy, hereditary sensory, type 1F Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Jul 11, 2019

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.1
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs200026815; hg19: chr11-63398530;