rs6820411

Positions:

• chr4-122924114-C-A

Variant summary

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

The NM_145207.3(SPATA5):​c.163+809C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0895 in 152,222 control chromosomes in the GnomAD database, including 817 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 0.089 (817 hom., cov: 32)
• Consequence: SPATA5 NM_145207.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA5	NM_145207.3	c.163+809C>A		intron_variant		ENST00000274008.5	NP_660208.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFG2A	ENST00000274008.5	c.163+809C>A		intron_variant		1	NM_145207.3	ENSP00000274008	P1
AFG2A	ENST00000422835.2	n.205+809C>A		intron_variant, non_coding_transcript_variant		1
AFG2A	ENST00000675612.1	c.163+809C>A		intron_variant				ENSP00000502453
AFG2A	ENST00000674886.1	n.228+809C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0896 AC: 13623 AN: 152104 Hom.: 816 Cov.: 32

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.0974

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0895 AC: 13623 AN: 152222 Hom.: 817 Cov.: 32 AF XY: 0.0861 AC XY: 6408 AN XY: 74440

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.0738

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0848

Gnomad4 FIN AF: 0.0974

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.104

Alfa AF: 0.109 Hom.: 130

Bravo AF: 0.0858

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs6820411; hg19: chr4-123845269;