chr13-36302566-C-T

Variant names:

• chr13-36302566-C-T
• rs9547190
• NM_015087.5:c.*1799G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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: Benign. The variant received -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 VariationId 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.

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.*1799G>A		3_prime_UTR	Exon 9 of 9	NP_055902.1	Q8N0X7
	SPART	NM_001142294.2		c.*1799G>A		3_prime_UTR	Exon 9 of 9	NP_001135766.1	Q8N0X7
	SPART	NM_001142295.2		c.*1799G>A		3_prime_UTR	Exon 9 of 9	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.*1799G>A		3_prime_UTR	Exon 9 of 9	ENSP00000406061.2	Q8N0X7
	SPART	ENST00000451493.5	TSL:1	c.*1799G>A		3_prime_UTR	Exon 9 of 9	ENSP00000414147.1	Q8N0X7
	SPART	ENST00000355182.8	TSL:5	c.*1799G>A		3_prime_UTR	Exon 9 of 9	ENSP00000347314.4	Q8N0X7

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.153 AC: 6351 AN: 41480

American (AMR) AF: 0.292 AC: 4459 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 765 AN: 3468

East Asian (EAS) AF: 0.510 AC: 2633 AN: 5162

South Asian (SAS) AF: 0.283 AC: 1362 AN: 4816

European-Finnish (FIN) AF: 0.230 AC: 2430 AN: 10572

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18214 AN: 67968

Other (OTH) AF: 0.221 AC: 467 AN: 2116

Alfa AF: 0.251 Hom.: 2697

Bravo AF: 0.242

Asia WGS AF: 0.400 AC: 1393 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Troyer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.41
PhyloP100		-0.085
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9547190; hg19: chr13-36876703;