rs1555059203

Variant names:

• chr11-63671329-ACA-CAG
• rs1555059203
• NM_015459.5:c.5_7delTGTinsCTG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015459.5(ATL3):​c.5_7delTGTinsCTG​(p.LeuSer2SerAla) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATL3 NM_015459.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATL3	NM_015459.5	c.5_7delTGTinsCTG	p.LeuSer2SerAla	missense_variant		ENST00000398868.8	NP_056274.3
ATL3	XM_047426725.1	c.161_163delTGTinsCTG	p.LeuSer54SerAla	missense_variant			XP_047282681.1
ATL3	XM_006718493.2	c.5_7delTGTinsCTG	p.LeuSer2SerAla	missense_variant			XP_006718556.1
ATL3	NM_001290048.2	c.-9+305_-9+307delTGTinsCTG		intron_variant	Intron 1 of 12		NP_001276977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATL3	ENST00000398868.8	c.5_7delTGTinsCTG	p.LeuSer2SerAla	missense_variant		1	NM_015459.5	ENSP00000381844.3
ATL3	ENST00000540699.1	c.161_163delTGTinsCTG	p.LeuSer54SerAla	missense_variant		3		ENSP00000441842.1
ATL3	ENST00000538786.1	c.-9+305_-9+307delTGTinsCTG		intron_variant	Intron 1 of 12	2		ENSP00000437593.1
ATL3	ENST00000535789.1	n.416_418delTGTinsCTG		non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neuropathy, hereditary sensory, type 1F Uncertain:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.5_7delinsCTG, is a complex sequence change that results in the deletion of 2 and insertion of 2 amino acid(s) in the ATL3 protein (p.Leu2_Ser3delinsSerAla). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with ATL3-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555059203; hg19: chr11-63438801;