13-36302210-ATACCT-A

Position:

• chr13-36302210-ATACCT-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BS1_Supporting

The NM_015087.5(SPART):​c.*2150_*2154delAGGTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 151,236 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0011 (1 hom., cov: 32)
• Consequence: SPART NM_015087.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.363

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00112 (169/151236) while in subpopulation AMR AF= 0.00106 (16/15046). AF 95% confidence interval is 0.000666. There are 1 homozygotes in gnomad4. There are 106 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPART	NM_015087.5	c.*2150_*2154delAGGTA		3_prime_UTR_variant	9/9	ENST00000438666.7	NP_055902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPART	ENST00000438666	c.*2150_*2154delAGGTA		3_prime_UTR_variant	9/9	1	NM_015087.5	ENSP00000406061.2
SPART	ENST00000451493	c.*2150_*2154delAGGTA		3_prime_UTR_variant	9/9	1		ENSP00000414147.1
SPART	ENST00000355182	c.*2150_*2154delAGGTA		3_prime_UTR_variant	9/9	5		ENSP00000347314.4
SPART	ENST00000650221	c.*2150_*2154delAGGTA		3_prime_UTR_variant	10/10			ENSP00000497209.1

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 169 AN: 151122 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000727

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00656

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000709

Gnomad OTH AF: 0.00289

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

GnomAD4 genome AF: 0.00112 AC: 169 AN: 151236 Hom.: 1 Cov.: 32 AF XY: 0.00144 AC XY: 106 AN XY: 73828

Gnomad4 AFR AF: 0.000724

Gnomad4 AMR AF: 0.00106

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00656

Gnomad4 NFE AF: 0.000709

Gnomad4 OTH AF: 0.00286

Alfa AF: 0.000432 Hom.: 0

Bravo AF: 0.000737

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Troyer syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs747194340; hg19: chr13-36876347;