Variant rs528012262 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_015459.5(ATL3):c.978+7_978+8insA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00954 in 1,610,820 control chromosomes in the GnomAD database, including 92 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 8 hom., cov: 30)

Exomes 𝑓: 0.0098 ( 84 hom. )

Consequence

ATL3
NM_015459.5 splice_region, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.267

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]

ATL3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 11-63636199-A-AT is Benign according to our data. Variant chr11-63636199-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 474841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1115 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ATL3	NM_015459.5 linkuse as main transcript	c.978+7_978+8insA	splice_region_variant, intron_variant	ENST00000398868.8	NP_056274.3
ATL3	NM_001290048.2 linkuse as main transcript	c.924+7_924+8insA	splice_region_variant, intron_variant		NP_001276977.1
ATL3	XM_006718493.2 linkuse as main transcript	c.921+7_921+8insA	splice_region_variant, intron_variant		XP_006718556.1
ATL3	XM_047426725.1 linkuse as main transcript	c.1134+7_1134+8insA	splice_region_variant, intron_variant		XP_047282681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATL3	ENST00000398868.8 linkuse as main transcript	c.978+7_978+8insA		splice_region_variant, intron_variant		1	NM_015459.5	ENSP00000381844
ATL3	ENST00000538786.1 linkuse as main transcript	c.924+7_924+8insA		splice_region_variant, intron_variant		2		ENSP00000437593	P1

Frequencies

GnomAD3 genomes

AF:

0.00734

AC:

1116

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00655

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.00529

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00631

AC:

1553

AN:

245946

Hom.:

AF XY:

0.00611

AC XY:

815

AN XY:

133354

show subpopulations

Gnomad AFR exome

AF:

0.00175

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.00202

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00138

Gnomad FIN exome

AF:

0.00534

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.00852

GnomAD4 exome

AF:

0.00977

AC:

14251

AN:

1458668

Hom.:

Cov.:

AF XY:

0.00951

AC XY:

6902

AN XY:

725534

show subpopulations

Gnomad4 AFR exome

AF:

0.00177

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.00212

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00197

Gnomad4 FIN exome

AF:

0.00577

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.00811

GnomAD4 genome

AF:

0.00733

AC:

1115

AN:

152152

Hom.:

Cov.:

AF XY:

0.00667

AC XY:

496

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00198

Gnomad4 AMR

AF:

0.00648

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00529

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00948

Hom.:

Bravo

AF:

0.00682

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.00871

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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	ATL3: BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over