13-36302022-A-G

Position:

• chr13-36302022-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015087.5(SPART):​c.*2343T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0592 in 152,256 control chromosomes in the GnomAD database, including 339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.059 (339 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPART NM_015087.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0180

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-36302022-A-G is Benign according to our data. Variant chr13-36302022-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 311737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPART	NM_015087.5	c.*2343T>C		3_prime_UTR_variant	9/9	ENST00000438666.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPART	ENST00000438666.7	c.*2343T>C		3_prime_UTR_variant	9/9	1	NM_015087.5	P1
SPART	ENST00000451493.5	c.*2343T>C		3_prime_UTR_variant	9/9	1		P1
SPART	ENST00000355182.8	c.*2343T>C		3_prime_UTR_variant	9/9	5		P1
SPART	ENST00000650221.1	c.*2343T>C		3_prime_UTR_variant	10/10			P1

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 9007 AN: 152138 Hom.: 338 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0972

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.0693

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.0592 AC: 9011 AN: 152256 Hom.: 339 Cov.: 32 AF XY: 0.0581 AC XY: 4327 AN XY: 74444

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0974

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0677

Gnomad4 NFE AF: 0.0836

Gnomad4 OTH AF: 0.0681

Alfa AF: 0.0699 Hom.: 102

Bravo AF: 0.0609

Asia WGS AF: 0.0150 AC: 53 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.77

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: rs34434389; hg19: chr13-36876159;