chr4-123146653-C-T

Position:

• chr4-123146653-C-T

Variant summary

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

The NM_145207.3(AFG2A):​c.2340+55948C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,092 control chromosomes in the GnomAD database, including 33,089 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 0.61 (33089 hom., cov: 32)
• Consequence: AFG2A NM_145207.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFG2A	NM_145207.3	c.2340+55948C>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.2340+55948C>T		intron_variant		1	NM_145207.3	ENSP00000274008.3
SPATA5	ENST00000675612.1	c.2409+55948C>T		intron_variant				ENSP00000502453.1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92652 AN: 151974 Hom.: 33077 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.609 AC: 92675 AN: 152092 Hom.: 33089 Cov.: 32 AF XY: 0.618 AC XY: 45979 AN XY: 74356

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.620

Alfa AF: 0.602 Hom.: 2532

Bravo AF: 0.579

Asia WGS AF: 0.789 AC: 2743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.58

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: rs303083; hg19: chr4-124067808;