rs778801809

chr13-36312448-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2 BP4_Strong BP6_Moderate BS1

The NM_015087.5(SPART):c.1513G>A(p.Val505Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000103 in 1,613,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: SPART NM_015087.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.45

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026564658).
• BP6: Variant 13-36312448-C-T is Benign according to our data. Variant chr13-36312448-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 461203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000105 (16/152072) while in subpopulation AMR AF= 0.000918 (14/15258). AF 95% confidence interval is 0.000554. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPART	NM_015087.5	c.1513G>A	p.Val505Ile	missense_variant	7/9	ENST00000438666.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPART	ENST00000438666.7	c.1513G>A	p.Val505Ile	missense_variant	7/9	1	NM_015087.5	P1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000918

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000505 AC: 127 AN: 251366 Hom.: 1 AF XY: 0.000486 AC XY: 66 AN XY: 135848

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000103 AC: 150 AN: 1461844 Hom.: 0 Cov.: 33 AF XY: 0.000103 AC XY: 75 AN XY: 727220

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00241

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.0000662

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152072 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74258

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000918

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000749 Hom.: 0

Bravo AF: 0.000264

ExAC AF: 0.000478 AC: 58

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 25, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.20
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.051	T;T;T;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.027	T;T;T;T;T
MetaSVM	Uncertain	0.69	D
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.38	N;N;N;.;.
REVEL	Uncertain	0.53
Sift	Benign	0.090	T;T;T;.;.
Sift4G	Pathogenic	0.0	D;D;D;.;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.16
MutPred		0.61		Gain of catalytic residue at N503 (P = 0.0186);Gain of catalytic residue at N503 (P = 0.0186);Gain of catalytic residue at N503 (P = 0.0186);Gain of catalytic residue at N503 (P = 0.0186);Gain of catalytic residue at N503 (P = 0.0186);
MVP		0.94
MPC		0.23
ClinPred		0.068	T
GERP RS		5.3
Varity_R		0.10
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs778801809; hg19: chr13-36886585; COSMIC: COSV62085567; COSMIC: COSV62085567;