chr15-64963545-T-T

Position:

• chr15-64963545-T-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

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. Variant has been reported in ClinVar as Benign (★).

• 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 15-64963545-T-T is Benign according to our data. Variant chr15-64963545-T-T is described in ClinVar as [Benign]. Clinvar id is 886280.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPG21	NM_016630.7	c.		exon_region	9/9	ENST00000204566.7	NP_057714.1
SPG21	NM_016630.7	c.		3_prime_UTR_variant	9/9	ENST00000204566.7	NP_057714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG21	ENST00000204566.7	c.		exon_region	9/9	1	NM_016630.7	ENSP00000204566.2
SPG21	ENST00000204566	c.		3_prime_UTR_variant	9/9	1	NM_016630.7	ENSP00000204566.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 15

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mast syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-65255886;