11-63630800-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_015459.5(ATL3):c.1539+239_1539+240insT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0073 (7 hom., cov: 0)
• Consequence: ATL3 NM_015459.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.39

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 -10 ACMG points.

• BP6: Variant 11-63630800-C-CA is Benign according to our data. Variant chr11-63630800-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 1300724.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00731 (803/109890) while in subpopulation AFR AF= 0.0251 (748/29788). AF 95% confidence interval is 0.0236. There are 7 homozygotes in gnomad4. There are 371 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd at 801 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATL3	NM_015459.5	c.1539+239_1539+240insT		intron_variant		ENST00000398868.8
ATL3	NM_001290048.2	c.1485+239_1485+240insT		intron_variant
ATL3	XM_006718493.2	c.1482+239_1482+240insT		intron_variant
ATL3	XM_047426725.1	c.1695+239_1695+240insT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATL3	ENST00000398868.8	c.1539+239_1539+240insT		intron_variant		1	NM_015459.5
ATL3	ENST00000538786.1	c.1485+239_1485+240insT		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.00729 AC: 801 AN: 109894 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00214

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000174

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000486

Gnomad OTH AF: 0.00418

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00731 AC: 803 AN: 109890 Hom.: 7 Cov.: 0 AF XY: 0.00713 AC XY: 371 AN XY: 52056

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.00214

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000174

Gnomad4 NFE AF: 0.000486

Gnomad4 OTH AF: 0.00417

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs58752695; hg19: chr11-63398272;