15-45406595-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024063.3(SPATA5L1):c.1275+1090T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,044 control chromosomes in the GnomAD database, including 27,396 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (27396 hom., cov: 32)
• Consequence: SPATA5L1 NM_024063.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA5L1	NM_024063.3	c.1275+1090T>G		intron_variant		ENST00000305560.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFG2B	ENST00000305560.11	c.1275+1090T>G		intron_variant		1	NM_024063.3	P1
AFG2B	ENST00000525552.1	c.48-434T>G		intron_variant, NMD_transcript_variant		3
AFG2B	ENST00000531970.5	c.1275+1090T>G		intron_variant, NMD_transcript_variant		2
AFG2B	ENST00000559860.2	n.1335+1090T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85151 AN: 151926 Hom.: 27337 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.557

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.561 AC: 85274 AN: 152044 Hom.: 27396 Cov.: 32 AF XY: 0.567 AC XY: 42159 AN XY: 74304

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.908

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.562

Alfa AF: 0.413 Hom.: 5928

Bravo AF: 0.592

Asia WGS AF: 0.737 AC: 2548 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	6.7
Dann	Benign	0.77

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: rs2467853; hg19: chr15-45698793;