chr15-64963545-T-T

Variant names:

• chr15-64963545-T-T
• NM_016630.7:c.

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016630.7(SPG21):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPG21 NM_016630.7 exon_region
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.723
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• mast syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016630.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPG21	NM_016630.7	MANE Select	c.		exon_region	Exon 9 of 9	NP_057714.1	Q9NZD8-1
	SPG21	NM_016630.7	MANE Select	c.		3_prime_UTR	Exon 9 of 9	NP_057714.1	Q9NZD8-1
	SPG21	NM_001127889.5		c.		exon_region	Exon 9 of 9	NP_001121361.1	Q9NZD8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPG21	ENST00000204566.7	TSL:1 MANE Select	c.		exon_region	Exon 9 of 9	ENSP00000204566.2	Q9NZD8-1
	SPG21	ENST00000433215.6	TSL:1	c.		exon_region	Exon 9 of 9	ENSP00000404111.2	Q9NZD8-1
	SPG21	ENST00000204566.7	TSL:1 MANE Select	c.		3_prime_UTR	Exon 9 of 9	ENSP00000204566.2	Q9NZD8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 15

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Mast syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72

Splicing

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

Other links and lift over

hg19: chr15-65255886;