rs201636843

chr11-63629346-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015459.5(ATL3):c.1599A>G(p.Arg533=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 1,614,128 control chromosomes in the GnomAD database, including 291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (12 hom., cov: 31)
  • Exomes 𝑓: 0.0046 (279 hom.)
• Consequence: ATL3 NM_015459.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.464

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-63629346-T-C is Benign according to our data. Variant chr11-63629346-T-C is described in ClinVar as [Benign]. Clinvar id is 474837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-63629346-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.464 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATL3	NM_015459.5	c.1599A>G	p.Arg533=	synonymous_variant	13/13	ENST00000398868.8
ATL3	NM_001290048.2	c.1545A>G	p.Arg515=	synonymous_variant	13/13
ATL3	XM_047426725.1	c.1755A>G	p.Arg585=	synonymous_variant	14/14
ATL3	XM_006718493.2	c.1542A>G	p.Arg514=	synonymous_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATL3	ENST00000398868.8	c.1599A>G	p.Arg533=	synonymous_variant	13/13	1	NM_015459.5
ATL3	ENST00000538786.1	c.1545A>G	p.Arg515=	synonymous_variant	13/13	2		P1

Frequencies

GnomAD3 genomes AF: 0.00264 AC: 402 AN: 152180 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0797

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00927 AC: 2313 AN: 249570 Hom.: 94 AF XY: 0.0123 AC XY: 1662 AN XY: 135406

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.0736

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000265

Gnomad OTH exome AF: 0.00396

GnomAD4 exome AF: 0.00464 AC: 6781 AN: 1461830 Hom.: 279 Cov.: 30 AF XY: 0.00669 AC XY: 4863 AN XY: 727220

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0727

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000119

Gnomad4 OTH exome AF: 0.00548

GnomAD4 genome AF: 0.00264 AC: 402 AN: 152298 Hom.: 12 Cov.: 31 AF XY: 0.00384 AC XY: 286 AN XY: 74480

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0798

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000528 Hom.: 0

Bravo AF: 0.000529

Asia WGS AF: 0.0350 AC: 120 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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	Invitae	Jan 31, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.5
Dann	Benign	0.38

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

Other links and lift over

dbSNP: rs201636843; hg19: chr11-63396818;