rs146683642

Positions:

• chr13-36304427-C-G
• chr13-36304427-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015087.5(SPART):​c.1939G>C​(p.Val647Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPART NM_015087.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058733553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPART	NM_015087.5	c.1939G>C	p.Val647Leu	missense_variant	9/9	ENST00000438666.7	NP_055902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPART	ENST00000438666.7	c.1939G>C	p.Val647Leu	missense_variant	9/9	1	NM_015087.5	ENSP00000406061	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000499 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.015
DANN	Benign	0.29
DEOGEN2	Benign	0.027	T;T;T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.48	.;.;T;.;.
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.059	T;T;T;T;T
MetaSVM	Benign	-0.75	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.0	N;N;N;.;.
REVEL	Benign	0.17
Sift	Benign	0.67	T;T;T;.;.
Sift4G	Benign	0.32	T;T;T;.;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.018
MutPred		0.20		Gain of catalytic residue at N646 (P = 0.027);Gain of catalytic residue at N646 (P = 0.027);Gain of catalytic residue at N646 (P = 0.027);Gain of catalytic residue at N646 (P = 0.027);Gain of catalytic residue at N646 (P = 0.027);
MVP		0.65
MPC		0.072
ClinPred		0.042	T
GERP RS		-9.4
Varity_R		0.025
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs146683642; hg19: chr13-36878564;