rs1369245036

Variant names:

• chr15-44628748-T-A
• NM_025137.4:c.1988A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-44628748-T-A
• chr15-44628748-T-C

Variant summary

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

The NM_025137.4(SPG11):​c.1988A>T​(p.Asp663Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,370 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPG11 NM_025137.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.941

Genes affected

SPG11 (HGNC:11226): (SPG11 vesicle trafficking associated, spatacsin) The protein encoded by this gene is a potential transmembrane protein that is phosphorylated upon DNA damage. Defects in this gene are a cause of spastic paraplegia type 11 (SPG11). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPG11	NM_025137.4	c.1988A>T	p.Asp663Val	missense_variant	Exon 10 of 40	ENST00000261866.12	NP_079413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPG11	ENST00000261866.12	c.1988A>T	p.Asp663Val	missense_variant	Exon 10 of 40	1	NM_025137.4	ENSP00000261866.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461370 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726986

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T;.;T;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.48	T;T;T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.1	M;M;.;M;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D
Polyphen		0.67	P;.;P;.;.
Vest4		0.50
MutPred		0.43		Gain of methylation at K660 (P = 0.0617);Gain of methylation at K660 (P = 0.0617);Gain of methylation at K660 (P = 0.0617);Gain of methylation at K660 (P = 0.0617);Gain of methylation at K660 (P = 0.0617);
MVP		0.68
MPC		0.31
ClinPred		0.88	D
GERP RS		4.0
Varity_R		0.13
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-44920946;