chr15-45402503-G-T

Position:

• chr15-45402503-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024063.3(SPATA5L1):​c.74G>T​(p.Gly25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA5L1 NM_024063.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.93

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA5L1	NM_024063.3	c.74G>T	p.Gly25Val	missense_variant	1/8	ENST00000305560.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFG2B	ENST00000305560.11	c.74G>T	p.Gly25Val	missense_variant	1/8	1	NM_024063.3	P1
AFG2B	ENST00000559860.2	n.134G>T		non_coding_transcript_exon_variant	1/5	2
AFG2B	ENST00000531970.5	c.74G>T	p.Gly25Val	missense_variant, NMD_transcript_variant	1/8	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455922 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 724066

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

The c.74G>T (p.G25V) alteration is located in exon 1 (coding exon 1) of the SPATA5L1 gene. This alteration results from a G to T substitution at nucleotide position 74, causing the glycine (G) at amino acid position 25 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Pathogenic	0.40	D
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.3	D;.
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0020	D;.
Sift4G	Pathogenic	0.0	D;.
Polyphen		0.97	D;.
Vest4		0.47
MutPred		0.36		Loss of relative solvent accessibility (P = 0.0306);Loss of relative solvent accessibility (P = 0.0306);
MVP		0.83
MPC		1.8
ClinPred		1.0	D
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.47
gMVP		0.86

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: chr15-45694701;