13-36326690-AT-CA

Variant names:

• chr13-36326690-AT-CA
• NM_015087.5:c.1172_1173delATinsTG
• SPART p.Asp391Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015087.5(SPART):​c.1172_1173delATinsTG​(p.Asp391Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D391G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPART NM_015087.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 0 publications found

Genes affected

SPART (HGNC:18514): (spartin) This gene encodes a protein containing a MIT (Microtubule Interacting and Trafficking molecule) domain, and is implicated in regulating endosomal trafficking and mitochondria function. The protein localizes to mitochondria and partially co-localizes with microtubules. Stimulation with epidermal growth factor (EGF) results in protein translocation to the plasma membrane, and the protein functions in the degradation and intracellular trafficking of EGF receptor. Multiple alternatively spliced variants, encoding the same protein, have been identified. Mutations associated with this gene cause autosomal recessive spastic paraplegia 20 (Troyer syndrome). [provided by RefSeq, Nov 2008]

SPART Gene-Disease associations (from GenCC):

• Troyer syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015087.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPART	NM_015087.5	MANE Select	c.1172_1173delATinsTG	p.Asp391Val	missense	N/A	NP_055902.1	Q8N0X7
	SPART	NM_001142294.2		c.1172_1173delATinsTG	p.Asp391Val	missense	N/A	NP_001135766.1	Q8N0X7
	SPART	NM_001142295.2		c.1172_1173delATinsTG	p.Asp391Val	missense	N/A	NP_001135767.1	Q8N0X7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPART	ENST00000438666.7	TSL:1 MANE Select	c.1172_1173delATinsTG	p.Asp391Val	missense	N/A	ENSP00000406061.2	Q8N0X7
	SPART	ENST00000451493.5	TSL:1	c.1172_1173delATinsTG	p.Asp391Val	missense	N/A	ENSP00000414147.1	Q8N0X7
	SPART	ENST00000494062.2	TSL:1	c.1172_1173delATinsTG	p.Asp391Val	missense	N/A	ENSP00000473599.1	Q8N0X7

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-36900827;