15-64965260-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000204566.7(SPG21):​c.810+60A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,607,742 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 30 hom., cov: 32)
Exomes 𝑓: 0.019 ( 291 hom. )

Consequence

SPG21
ENST00000204566.7 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.980
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 15-64965260-T-G is Benign according to our data. Variant chr15-64965260-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1212151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0167 (2536/152294) while in subpopulation AMR AF= 0.0237 (362/15298). AF 95% confidence interval is 0.0217. There are 30 homozygotes in gnomad4. There are 1324 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPG21NM_016630.7 linkuse as main transcriptc.810+60A>C intron_variant ENST00000204566.7 NP_057714.1
SPG21NM_001127889.5 linkuse as main transcriptc.810+60A>C intron_variant NP_001121361.1
SPG21NM_001127890.5 linkuse as main transcriptc.729+60A>C intron_variant NP_001121362.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPG21ENST00000204566.7 linkuse as main transcriptc.810+60A>C intron_variant 1 NM_016630.7 ENSP00000204566 P1Q9NZD8-1

Frequencies

GnomAD3 genomes
AF:
0.0166
AC:
2533
AN:
152176
Hom.:
30
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00384
Gnomad AMI
AF:
0.0362
Gnomad AMR
AF:
0.0237
Gnomad ASJ
AF:
0.0389
Gnomad EAS
AF:
0.00654
Gnomad SAS
AF:
0.00849
Gnomad FIN
AF:
0.0355
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0197
Gnomad OTH
AF:
0.0234
GnomAD4 exome
AF:
0.0188
AC:
27346
AN:
1455448
Hom.:
291
AF XY:
0.0187
AC XY:
13524
AN XY:
724446
show subpopulations
Gnomad4 AFR exome
AF:
0.00258
Gnomad4 AMR exome
AF:
0.0145
Gnomad4 ASJ exome
AF:
0.0385
Gnomad4 EAS exome
AF:
0.00232
Gnomad4 SAS exome
AF:
0.00688
Gnomad4 FIN exome
AF:
0.0269
Gnomad4 NFE exome
AF:
0.0201
Gnomad4 OTH exome
AF:
0.0186
GnomAD4 genome
AF:
0.0167
AC:
2536
AN:
152294
Hom.:
30
Cov.:
32
AF XY:
0.0178
AC XY:
1324
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.00382
Gnomad4 AMR
AF:
0.0237
Gnomad4 ASJ
AF:
0.0389
Gnomad4 EAS
AF:
0.00675
Gnomad4 SAS
AF:
0.00871
Gnomad4 FIN
AF:
0.0355
Gnomad4 NFE
AF:
0.0197
Gnomad4 OTH
AF:
0.0237
Alfa
AF:
0.0147
Hom.:
3
Bravo
AF:
0.0149
Asia WGS
AF:
0.0100
AC:
36
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 28, 2018- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.55
DANN
Benign
0.75

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs72740676; hg19: chr15-65257601; API