rs11098682

Positions:

• chr4-122947124-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145207.3(AFG2A):​c.1459-109G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 1,082,886 control chromosomes in the GnomAD database, including 415,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (47056 hom., cov: 32)
  • Exomes 𝑓: 0.89 (368851 hom.)
• Consequence: AFG2A NM_145207.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0300

Genes affected

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-122947124-G-T is Benign according to our data. Variant chr4-122947124-G-T is described in ClinVar as [Benign]. Clinvar id is 586674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFG2A	NM_145207.3	c.1459-109G>T		intron_variant		ENST00000274008.5	NP_660208.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA5	ENST00000274008.5	c.1459-109G>T		intron_variant		1	NM_145207.3	ENSP00000274008.3
SPATA5	ENST00000422835.2	n.1501-109G>T		intron_variant		1
SPATA5	ENST00000675612.1	c.1456-109G>T		intron_variant				ENSP00000502453.1
SPATA5	ENST00000674886.1	n.1521-109G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115041 AN: 151976 Hom.: 47036 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.770

GnomAD4 exome AF: 0.886 AC: 825037 AN: 930792 Hom.: 368851 AF XY: 0.888 AC XY: 408763 AN XY: 460484

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.804

Gnomad4 ASJ exome AF: 0.856

Gnomad4 EAS exome AF: 0.948

Gnomad4 SAS exome AF: 0.896

Gnomad4 FIN exome AF: 0.904

Gnomad4 NFE exome AF: 0.901

Gnomad4 OTH exome AF: 0.864

GnomAD4 genome AF: 0.757 AC: 115110 AN: 152094 Hom.: 47056 Cov.: 32 AF XY: 0.761 AC XY: 56565 AN XY: 74372

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.862

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.894

Gnomad4 FIN AF: 0.905

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.773

Alfa AF: 0.857 Hom.: 27828

Bravo AF: 0.732

Asia WGS AF: 0.901 AC: 3129 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.33

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: rs11098682; hg19: chr4-123868279;