chr15-45402832-G-A

Position:

• chr15-45402832-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024063.3(SPATA5L1):​c.403G>A​(p.Ala135Thr) 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 benign 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: 3.11

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2139467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA5L1	NM_024063.3	c.403G>A	p.Ala135Thr	missense_variant	1/8	ENST00000305560.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFG2B	ENST00000305560.11	c.403G>A	p.Ala135Thr	missense_variant	1/8	1	NM_024063.3	P1
AFG2B	ENST00000559860.2	n.463G>A		non_coding_transcript_exon_variant	1/5	2
AFG2B	ENST00000531970.5	c.403G>A	p.Ala135Thr	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: 1445432 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 719516

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

Jan 04, 2024

The c.403G>A (p.A135T) alteration is located in exon 1 (coding exon 1) of the SPATA5L1 gene. This alteration results from a G to A substitution at nucleotide position 403, causing the alanine (A) at amino acid position 135 to be replaced by a threonine (T). 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	Benign	0.11
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.73	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.52	N;.
REVEL	Benign	0.21
Sift	Benign	0.23	T;.
Sift4G	Benign	0.34	T;.
Polyphen		0.19	B;.
Vest4		0.14
MutPred		0.43		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.91
MPC		1.0
ClinPred		0.36	T
GERP RS		3.8
Varity_R		0.081
gMVP		0.50

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: chr15-45695030;