Genetic Variant ENST00000451493.5:c.-202G>C (chr13-36346781-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.150

Publications

6 publications found

Variant links:

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 links:

SPART-AS1 (HGNC:39933): (SPART antisense RNA 1)

SPART-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1526321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000451493.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
SPART	NM_001142294.2	c.-2-10949G>C	intron	N/A	NP_001135766.1	Q8N0X7
SPART-AS1	NR_045180.1	n.77+274C>G	intron	N/A
SPART-AS1	NR_045181.1	n.77+274C>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPART	ENST00000451493.5	TSL:1	c.-202G>C	5_prime_UTR	Exon 1 of 9	ENSP00000414147.1	Q8N0X7
SPART	ENST00000355182.8	TSL:5	c.-2-10949G>C	intron	N/A	ENSP00000347314.4	Q8N0X7
SPART	ENST00000650221.1		c.-2-10949G>C	intron	N/A	ENSP00000497209.1	Q8N0X7

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37763

AN:

152066

Hom.:

5232

Cov.:

show subpopulations

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:

AN:

202

Hom.:

Cov.:

AF XY:

0.375

AC XY:

AN XY:

152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.417

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.395

AC:

AN:

162

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.559

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.248

AC:

37775

AN:

152184

Hom.:

5228

Cov.:

AF XY:

0.250

AC XY:

18618

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.141

AC:

5845

AN:

41550

American (AMR)

AF:

0.298

AC:

4555

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

773

AN:

3472

East Asian (EAS)

AF:

0.512

AC:

2637

AN:

5150

South Asian (SAS)

AF:

0.288

AC:

1391

AN:

4830

European-Finnish (FIN)

AF:

0.234

AC:

2476

AN:

10596

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.284

AC:

19284

AN:

67984

Other (OTH)

AF:

0.225

AC:

473

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1463

2925

4388

5850

7313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.252

Hom.:

651

Bravo

AF:

0.247

Asia WGS

AF:

0.402

AC:

1399

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

6.8

(source)

DANN

Benign

0.67

PhyloP100

-0.15

PromoterAI

-0.31

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over