4-123096501-G-C

Position:

• chr4-123096501-G-C

Variant summary

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

The NM_145207.3(SPATA5):​c.2340+5796G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 151,858 control chromosomes in the GnomAD database, including 41,052 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 0.73 (41052 hom., cov: 31)
• Consequence: SPATA5 NM_145207.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

Genes affected

SPATA5 (HGNC:):

AFG2A (HGNC:18119): (AFG2 AAA ATPase homolog A) This gene encodes a member of the ATPase associated with diverse activities family, whose members are defined by a highly conserved ATPase domain. Members of this family participate in diverse cellular processes that include membrane fusion, DNA replication, microtubule severing, and protein degradation. The protein encoded by this gene has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Allelic variants in this gene have been associated with epilepsy, hearing loss, and cognitive disability syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA5	NM_145207.3	c.2340+5796G>C		intron_variant		ENST00000274008.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFG2A	ENST00000274008.5	c.2340+5796G>C		intron_variant		1	NM_145207.3	P1
AFG2A	ENST00000422835.2	n.2383-5683G>C		intron_variant, non_coding_transcript_variant		1
AFG2A	ENST00000675612.1	c.2409+5796G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110838 AN: 151740 Hom.: 41028 Cov.: 31

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.730 AC: 110905 AN: 151858 Hom.: 41052 Cov.: 31 AF XY: 0.738 AC XY: 54752 AN XY: 74234

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.711

Alfa AF: 0.745 Hom.: 4998

Bravo AF: 0.716

Asia WGS AF: 0.867 AC: 3014 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.1
DANN	Benign	0.36

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: rs307022; hg19: chr4-124017656;