chr13-36346781-C-G

Position:

• chr13-36346781-C-G

Variant summary

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

The ENST00000451493.5(SPART):​c.-202G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,386 control chromosomes in the GnomAD database, including 5,246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5228 hom., cov: 32)
  • Exomes 𝑓: 0.40 (18 hom.)
• Consequence: SPART ENST00000451493.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.150

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=-1.02).
• BP6: Variant 13-36346781-C-G is Benign according to our data. Variant chr13-36346781-C-G is described in ClinVar as [Benign]. Clinvar id is 1526321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-36346781-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPART	NM_001142294.2	c.-2-10949G>C		intron_variant			NP_001135766.1
SPART-AS1	NR_045180.1	n.77+274C>G		intron_variant
SPART-AS1	NR_045181.1	n.77+274C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPART	ENST00000451493.5	c.-202G>C		5_prime_UTR_variant	1/9	1		ENSP00000414147.1
SPART	ENST00000355182.8	c.-2-10949G>C		intron_variant		5		ENSP00000347314.4
SPART	ENST00000650221.1	c.-2-10949G>C		intron_variant				ENSP00000497209.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37763 AN: 152066 Hom.: 5232 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.401 AC: 81 AN: 202 Hom.: 18 Cov.: 0 AF XY: 0.375 AC XY: 57 AN XY: 152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.395

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.248 AC: 37775 AN: 152184 Hom.: 5228 Cov.: 32 AF XY: 0.250 AC XY: 18618 AN XY: 74408

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.225

Alfa AF: 0.252 Hom.: 651

Bravo AF: 0.247

Asia WGS AF: 0.402 AC: 1399 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.8
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9531842; hg19: chr13-36920918;