15-45402610-G-C

Variant names:

• chr15-45402610-G-C
• rs1171334745
• NM_024063.3:c.181G>C

Variant summary

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

The NM_024063.3(AFG2B):​c.181G>C​(p.Ala61Pro) 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AFG2B NM_024063.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81

Genes affected

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, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFG2B	NM_024063.3	c.181G>C	p.Ala61Pro	missense_variant	Exon 1 of 8	ENST00000305560.11	NP_076968.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA5L1	ENST00000305560.11	c.181G>C	p.Ala61Pro	missense_variant	Exon 1 of 8	1	NM_024063.3	ENSP00000305494.6
SPATA5L1	ENST00000531970.5	n.181G>C		non_coding_transcript_exon_variant	Exon 1 of 8	2		ENSP00000436823.1
SPATA5L1	ENST00000559860.2	n.241G>C		non_coding_transcript_exon_variant	Exon 1 of 5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1423130 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 705586

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

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Nov 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.181G>C (p.A61P) alteration is located in exon 1 (coding exon 1) of the SPATA5L1 gene. This alteration results from a G to C substitution at nucleotide position 181, causing the alanine (A) at amino acid position 61 to be replaced by a proline (P). 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	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Pathogenic	0.42	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.3	D;.
REVEL	Pathogenic	0.67
Sift	Uncertain	0.024	D;.
Sift4G	Benign	0.072	T;.
Polyphen		0.98	D;.
Vest4		0.59
MutPred		0.59		Loss of catalytic residue at A61 (P = 0.0069);Loss of catalytic residue at A61 (P = 0.0069);
MVP		0.89
MPC		2.1
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.90
gMVP		0.94

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

LitVar

Other links and lift over

dbSNP: rs1171334745; hg19: chr15-45694808;