14-50587757-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015915.5(ATL1):c.35-74G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 1,591,626 control chromosomes in the GnomAD database, including 1,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (104 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1653 hom.)
• Consequence: ATL1 NM_015915.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.387

Genes affected

ATL1 (HGNC:11231): (atlastin GTPase 1) The protein encoded by this gene is a GTPase and a Golgi body transmembrane protein. The encoded protein can form a homotetramer and has been shown to interact with spastin and with mitogen-activated protein kinase kinase kinase kinase 4. This protein may be involved in axonal maintenance as evidenced by the fact that defects in this gene are a cause of spastic paraplegia type 3. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-50587757-G-C is Benign according to our data. Variant chr14-50587757-G-C is described in ClinVar as [Benign]. Clinvar id is 1262532.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATL1	NM_015915.5	c.35-74G>C		intron_variant		ENST00000358385.12
ATL1	NM_001127713.1	c.35-74G>C		intron_variant
ATL1	NM_181598.4	c.35-74G>C		intron_variant
ATL1	XM_047431430.1	c.35-74G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATL1	ENST00000358385.12	c.35-74G>C		intron_variant		1	NM_015915.5	P3

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5711 AN: 152132 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.0396

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0488

Gnomad OTH AF: 0.0459

GnomAD4 exome AF: 0.0439 AC: 63209 AN: 1439376 Hom.: 1653 AF XY: 0.0435 AC XY: 31249 AN XY: 717642

Gnomad4 AFR exome AF: 0.0224

Gnomad4 AMR exome AF: 0.0281

Gnomad4 ASJ exome AF: 0.0384

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0117

Gnomad4 FIN exome AF: 0.0357

Gnomad4 NFE exome AF: 0.0499

Gnomad4 OTH exome AF: 0.0402

GnomAD4 genome AF: 0.0376 AC: 5720 AN: 152250 Hom.: 104 Cov.: 32 AF XY: 0.0374 AC XY: 2783 AN XY: 74440

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.0395

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.0488

Gnomad4 OTH AF: 0.0454

Alfa AF: 0.0232 Hom.: 12

Bravo AF: 0.0362

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.42
Dann	Benign	0.41

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: rs77224287; hg19: chr14-51054475;