chr13-36302566-C-T

Position:

• chr13-36302566-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015087.5(SPART):​c.*1799G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,084 control chromosomes in the GnomAD database, including 4,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4910 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SPART NM_015087.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0850

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 13-36302566-C-T is Benign according to our data. Variant chr13-36302566-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 311746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPART	NM_015087.5	c.*1799G>A		3_prime_UTR_variant	9/9	ENST00000438666.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPART	ENST00000438666.7	c.*1799G>A		3_prime_UTR_variant	9/9	1	NM_015087.5	P1
SPART	ENST00000451493.5	c.*1799G>A		3_prime_UTR_variant	9/9	1		P1
SPART	ENST00000355182.8	c.*1799G>A		3_prime_UTR_variant	9/9	5		P1
SPART	ENST00000650221.1	c.*1799G>A		3_prime_UTR_variant	10/10			P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36987 AN: 151960 Hom.: 4914 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.243 AC: 37006 AN: 152080 Hom.: 4910 Cov.: 32 AF XY: 0.246 AC XY: 18308 AN XY: 74352

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.221

Alfa AF: 0.256 Hom.: 2346

Bravo AF: 0.242

Asia WGS AF: 0.400 AC: 1393 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Troyer syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
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: rs9547190; hg19: chr13-36876703;