Variant rs752274594 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong

The NM_145207.3(AFG2A):c.1334+6_1334+9delCTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000721 in 1,594,816 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

AFG2A
NM_145207.3 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.34

Variant links:

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]

AFG2A links:

SPATA5 (HGNC:):

SPATA5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 4-122936160-CTCTT-C is Benign according to our data. Variant chr4-122936160-CTCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 475718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFG2A	NM_145207.3 linkuse as main transcript	c.1334+6_1334+9delCTTT		splice_region_variant, intron_variant		ENST00000274008.5	NP_660208.2	Q8NB90-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SPATA5	ENST00000274008.5 linkuse as main transcript	c.1334+6_1334+9delCTTT	splice_region_variant, intron_variant	1	NM_145207.3	ENSP00000274008.3	Q8NB90-1
SPATA5	ENST00000422835.2 linkuse as main transcript	n.1376+6_1376+9delCTTT	splice_region_variant, intron_variant	1
SPATA5	ENST00000675612.1 linkuse as main transcript	c.1331+6_1331+9delCTTT	splice_region_variant, intron_variant			ENSP00000502453.1	A0A6Q8PGU6
SPATA5	ENST00000674886.1 linkuse as main transcript	n.1396+6_1396+9delCTTT	splice_region_variant, intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000422

AC:

102

AN:

241730

Hom.:

AF XY:

0.000337

AC XY:

AN XY:

130584

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00153

GnomAD4 exome

AF:

0.0000762

AC:

110

AN:

1442758

Hom.:

AF XY:

0.0000670

AC XY:

AN XY:

716950

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000504

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000106

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 26, 2023

See Variant Classification Assertion Criteria. -

Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 27, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over