chr15-45402514-T-G

Position:

• chr15-45402514-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PS1_Moderate PM2 PP3_Moderate PP5

The NM_024063.3(SPATA5L1):​c.85T>G​(p.Cys29Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPATA5L1 NM_024063.3 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.68

Genes affected

SPATA5L1 (HGNC:):

AFG2B (HGNC:28762): (AFG2 AAA ATPase homolog B) Predicted to enable ATP binding activity. Located in cytoplasm and spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PS1: Transcript NM_024063.3 (SPATA5L1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859
• PP5: Variant 15-45402514-T-G is Pathogenic according to our data. Variant chr15-45402514-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1210112.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA5L1	NM_024063.3	c.85T>G	p.Cys29Gly	missense_variant	1/8	ENST00000305560.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFG2B	ENST00000305560.11	c.85T>G	p.Cys29Gly	missense_variant	1/8	1	NM_024063.3	P1
AFG2B	ENST00000559860.2	n.145T>G		non_coding_transcript_exon_variant	1/5	2
AFG2B	ENST00000531970.5	c.85T>G	p.Cys29Gly	missense_variant, NMD_transcript_variant	1/8	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

See cases Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Houlden Lab, UCL Institute of Neurology

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Pathogenic	0.38	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Uncertain	0.72	D
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	D
PROVEAN	Pathogenic	-5.0	D;.
REVEL	Pathogenic	0.83
Sift	Benign	0.079	T;.
Sift4G	Benign	0.14	T;.
Polyphen		0.97	D;.
Vest4		0.85
MutPred		0.57		Loss of stability (P = 0.0037);Loss of stability (P = 0.0037);
MVP		0.83
MPC		2.2
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.82
gMVP		0.91

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: chr15-45694712;