13-36346475-C-T

Position:

• chr13-36346475-C-T

Variant summary

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

The ENST00000494062.2(SPART):​c.-236G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,766 control chromosomes in the GnomAD database, including 5,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5215 hom., cov: 32)
  • Exomes 𝑓: 0.26 (25 hom.)
• Consequence: SPART ENST00000494062.2 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.431

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-36346475-C-T is Benign according to our data. Variant chr13-36346475-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 311776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPART	NM_001142294.2	c.-2-10643G>A		intron_variant			NP_001135766.1
SPART	NM_001142295.2	c.-3+107G>A		intron_variant			NP_001135767.1
SPART	XM_005266314.4	c.-75+107G>A		intron_variant			XP_005266371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPART	ENST00000494062.2	c.-236G>A		5_prime_UTR_variant	1/10	1		ENSP00000473599.1
SPART	ENST00000451493.5	c.-3+107G>A		intron_variant		1		ENSP00000414147.1
SPART	ENST00000355182.8	c.-2-10643G>A		intron_variant		5		ENSP00000347314.4

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37796 AN: 151980 Hom.: 5220 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.260 AC: 176 AN: 676 Hom.: 25 Cov.: 0 AF XY: 0.283 AC XY: 146 AN XY: 516

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.249 AC: 37809 AN: 152090 Hom.: 5215 Cov.: 32 AF XY: 0.250 AC XY: 18617 AN XY: 74336

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.224

Alfa AF: 0.134 Hom.: 259

Bravo AF: 0.247

Asia WGS AF: 0.401 AC: 1395 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 28, 2022	- -

Troyer syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.5
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2281864; hg19: chr13-36920612;