NM_015087.5:c.*2127_*2130delGATA

Variant names:

• chr13-36302234-TTATC-T
• rs150662490
• NM_015087.5:c.*2127_*2130delGATA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015087.5(SPART):​c.*2127_*2130delGATA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,704 control chromosomes in the GnomAD database, including 4,761 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4761 hom., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: SPART NM_015087.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00700
• Publications: 2 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 -10 ACMG points.

• BP6: Variant 13-36302234-TTATC-T is Benign according to our data. Variant chr13-36302234-TTATC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 311742.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 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.*2127_*2130delGATA		3_prime_UTR	Exon 9 of 9	NP_055902.1	Q8N0X7
	SPART	NM_001142294.2		c.*2127_*2130delGATA		3_prime_UTR	Exon 9 of 9	NP_001135766.1	Q8N0X7
	SPART	NM_001142295.2		c.*2127_*2130delGATA		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.*2127_*2130delGATA		3_prime_UTR	Exon 9 of 9	ENSP00000406061.2	Q8N0X7
	SPART	ENST00000451493.5	TSL:1	c.*2127_*2130delGATA		3_prime_UTR	Exon 9 of 9	ENSP00000414147.1	Q8N0X7
	SPART	ENST00000355182.8	TSL:5	c.*2127_*2130delGATA		3_prime_UTR	Exon 9 of 9	ENSP00000347314.4	Q8N0X7

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36663 AN: 151586 Hom.: 4766 Cov.: 24

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.216

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.242 AC: 36680 AN: 151704 Hom.: 4761 Cov.: 24 AF XY: 0.244 AC XY: 18115 AN XY: 74118

African (AFR) AF: 0.152 AC: 6313 AN: 41436

American (AMR) AF: 0.290 AC: 4426 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 761 AN: 3458

East Asian (EAS) AF: 0.503 AC: 2559 AN: 5086

South Asian (SAS) AF: 0.280 AC: 1349 AN: 4816

European-Finnish (FIN) AF: 0.228 AC: 2403 AN: 10532

Middle Eastern (MID) AF: 0.194 AC: 55 AN: 284

European-Non Finnish (NFE) AF: 0.267 AC: 18092 AN: 67832

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

Alfa AF: 0.242 Hom.: 575

Bravo AF: 0.241

Asia WGS AF: 0.399 AC: 1389 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Troyer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.0070
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: rs150662490; hg19: chr13-36876371; COSMIC: COSV53482476; COSMIC: COSV53482476;