chr15-64974736-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_016630.7(SPG21):ā€‹c.318T>Cā€‹(p.Phe106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000616 in 1,614,180 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0036 ( 7 hom., cov: 32)
Exomes š‘“: 0.00030 ( 2 hom. )

Consequence

SPG21
NM_016630.7 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.00
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 -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 15-64974736-A-G is Benign according to our data. Variant chr15-64974736-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 415528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPG21NM_016630.7 linkuse as main transcriptc.318T>C p.Phe106= synonymous_variant 5/9 ENST00000204566.7
SPG21NM_001127889.5 linkuse as main transcriptc.318T>C p.Phe106= synonymous_variant 5/9
SPG21NM_001127890.5 linkuse as main transcriptc.237T>C p.Phe79= synonymous_variant 4/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SPG21ENST00000204566.7 linkuse as main transcriptc.318T>C p.Phe106= synonymous_variant 5/91 NM_016630.7 P1Q9NZD8-1

Frequencies

GnomAD3 genomes
AF:
0.00362
AC:
551
AN:
152204
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0128
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.000796
AC:
200
AN:
251300
Hom.:
0
AF XY:
0.000523
AC XY:
71
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.0118
Gnomad AMR exome
AF:
0.000231
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000304
AC:
444
AN:
1461858
Hom.:
2
Cov.:
31
AF XY:
0.000245
AC XY:
178
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0118
Gnomad4 AMR exome
AF:
0.000380
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:
0.00000180
Gnomad4 OTH exome
AF:
0.000497
GnomAD4 genome
AF:
0.00362
AC:
551
AN:
152322
Hom.:
7
Cov.:
32
AF XY:
0.00349
AC XY:
260
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0127
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00277
Hom.:
1
Bravo
AF:
0.00369
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxFeb 22, 2021- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsDec 29, 2016- -
Mast syndrome Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
7.9
DANN
Benign
0.63

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: rs147236778; hg19: chr15-65267074; API