13-36346475-C-T

Variant names:

• chr13-36346475-C-T
• rs2281864
• ENST00000494062.2:c.-236G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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-AS1 (HGNC:39933): (SPART antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000494062.2. 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_001142294.2		c.-2-10643G>A		intron	N/A	NP_001135766.1	Q8N0X7
	SPART	NM_001142295.2		c.-3+107G>A		intron	N/A	NP_001135767.1	Q8N0X7
	SPART-AS1	NR_045180.1		n.45C>T		non_coding_transcript_exon	Exon 1 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPART	ENST00000494062.2	TSL:1	c.-236G>A		5_prime_UTR	Exon 1 of 10	ENSP00000473599.1	Q8N0X7
	SPART	ENST00000451493.5	TSL:1	c.-3+107G>A		intron	N/A	ENSP00000414147.1	Q8N0X7
	SPART	ENST00000888914.1		c.-238G>A		5_prime_UTR	Exon 1 of 9	ENSP00000558973.1

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

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 2 AN: 10

East Asian (EAS) AF: 0.417 AC: 5 AN: 12

South Asian (SAS) AF: 0.200 AC: 10 AN: 50

European-Finnish (FIN) AF: 0.167 AC: 2 AN: 12

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.270 AC: 150 AN: 556

Other (OTH) AF: 0.250 AC: 6 AN: 24

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

African (AFR) AF: 0.143 AC: 5938 AN: 41536

American (AMR) AF: 0.298 AC: 4554 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 773 AN: 3472

East Asian (EAS) AF: 0.511 AC: 2628 AN: 5142

South Asian (SAS) AF: 0.288 AC: 1389 AN: 4820

European-Finnish (FIN) AF: 0.233 AC: 2461 AN: 10574

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.283 AC: 19255 AN: 67938

Other (OTH) AF: 0.224 AC: 472 AN: 2108

Alfa AF: 0.134 Hom.: 259

Bravo AF: 0.247

Asia WGS AF: 0.401 AC: 1395 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Troyer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.5
DANN	Benign	0.90
PhyloP100		0.43
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2281864; hg19: chr13-36920612;