Variant chr15-64963727-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000204566.7(SPG21):c.820C>A(p.Leu274Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SPG21
ENST00000204566.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25

Variant links:

Genes affected

SPG21 (HGNC:20373): (SPG21 abhydrolase domain containing, maspardin) The protein encoded by this gene binds to the hydrophobic C-terminal amino acids of CD4 which are involved in repression of T cell activation. The interaction with CD4 is mediated by the noncatalytic alpha/beta hydrolase fold domain of this protein. It is thus proposed that this gene product modulates the stimulatory activity of CD4. Mutations in this gene are associated with autosomal recessive spastic paraplegia 21 (SPG21), also known as mast syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

SPG21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21382466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SPG21	NM_016630.7 linkuse as main transcript	c.820C>A	p.Leu274Met	missense_variant	9/9	ENST00000204566.7	NP_057714.1
SPG21	NM_001127889.5 linkuse as main transcript	c.820C>A	p.Leu274Met	missense_variant	9/9		NP_001121361.1
SPG21	NM_001127890.5 linkuse as main transcript	c.739C>A	p.Leu247Met	missense_variant	8/8		NP_001121362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG21	ENST00000204566.7 linkuse as main transcript	c.820C>A	p.Leu274Met	missense_variant	9/9	1	NM_016630.7	ENSP00000204566	P1	Q9NZD8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461160

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Sep 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;.;T;.

Eigen

Benign

0.052

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

.;D;D;D

M_CAP

Benign

0.0044

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.34

N;.;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.59

N;N;N;N

REVEL

Benign

0.074

Sift

Benign

0.11

T;T;T;T

Sift4G

Benign

0.086

T;T;T;T

Polyphen

0.014

B;.;B;B

Vest4

0.33

MutPred

0.42

Loss of helix (P = 0.1299);.;Loss of helix (P = 0.1299);.;

MVP

0.27

MPC

0.32

ClinPred

0.55

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over