Variant rs796051893 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5

The NM_145207.3(SPATA5):c.269G>A(p.Ser90Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,702 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S90I) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPATA5
NM_145207.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.75

Variant links:

Genes affected

SPATA5 (HGNC:):

SPATA5 links:

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA5	NM_145207.3 linkuse as main transcript	c.269G>A	p.Ser90Asn	missense_variant	2/16	ENST00000274008.5	NP_660208.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFG2A	ENST00000274008.5 linkuse as main transcript	c.269G>A	p.Ser90Asn	missense_variant	2/16	1	NM_145207.3	ENSP00000274008	P1	Q8NB90-1
AFG2A	ENST00000422835.2 linkuse as main transcript	n.311G>A		non_coding_transcript_exon_variant	2/15	1
AFG2A	ENST00000675612.1 linkuse as main transcript	c.266G>A	p.Ser89Asn	missense_variant	2/17			ENSP00000502453
AFG2A	ENST00000674886.1 linkuse as main transcript	n.331G>A		non_coding_transcript_exon_variant	2/11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250330

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000164

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460702

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726596

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000659

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.089

MetaRNN

Uncertain

0.53

MetaSVM

Uncertain

0.34

MutationTaster

Benign

0.73

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.46

MutPred

0.37

Gain of loop (P = 0.069);

MVP

0.86

MPC

0.50

ClinPred

0.86

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.62

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over