rs176708

Positions:

• chrX-130143913-G-T

Variant summary

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

The NM_004208.4(AIFM1):​c.696+1566C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 109,968 control chromosomes in the GnomAD database, including 10,291 homozygotes. There are 15,636 hemizygotes in GnomAD. 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 0.49 (10291 hom., 15636 hem., cov: 22)
• Consequence: AIFM1 NM_004208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

Genes affected

AIFM1 (HGNC:8768): (apoptosis inducing factor mitochondria associated 1) This gene encodes a flavoprotein essential for nuclear disassembly in apoptotic cells, and it is found in the mitochondrial intermembrane space in healthy cells. Induction of apoptosis results in the translocation of this protein to the nucleus where it affects chromosome condensation and fragmentation. In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. Mutations in this gene cause combined oxidative phosphorylation deficiency 6 (COXPD6), a severe mitochondrial encephalomyopathy, as well as Cowchock syndrome, also known as X-linked recessive Charcot-Marie-Tooth disease-4 (CMTX-4), a disorder resulting in neuropathy, and axonal and motor-sensory defects with deafness and cognitive disability. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 10. [provided by RefSeq, Aug 2015]

RAB33A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIFM1	NM_004208.4	c.696+1566C>A		intron_variant		ENST00000287295.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIFM1	ENST00000287295.8	c.696+1566C>A		intron_variant		1	NM_004208.4

Frequencies

GnomAD3 genomes AF: 0.491 AC: 53931 AN: 109919 Hom.: 10284 Cov.: 22 AF XY: 0.484 AC XY: 15597 AN XY: 32247

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.448

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.491 AC: 53974 AN: 109968 Hom.: 10291 Cov.: 22 AF XY: 0.484 AC XY: 15636 AN XY: 32306

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.487

Alfa AF: 0.442 Hom.: 5170

Bravo AF: 0.499

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.41

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: rs176708; hg19: chrX-129277888;