Variant rs17006342 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_145207.3(SPATA5):c.807G>T(p.Leu269=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 1,614,158 control chromosomes in the GnomAD database, including 1,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 124 hom., cov: 33)

Exomes 𝑓: 0.040 ( 1410 hom. )

Consequence

SPATA5
NM_145207.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.111

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-122934398-G-T is Benign according to our data. Variant chr4-122934398-G-T is described in ClinVar as [Benign]. Clinvar id is 475735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.111 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0306 (4657/152274) while in subpopulation NFE AF= 0.0417 (2837/68014). AF 95% confidence interval is 0.0404. There are 124 homozygotes in gnomad4. There are 2452 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 124 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA5	NM_145207.3 linkuse as main transcript	c.807G>T	p.Leu269=	synonymous_variant	5/16	ENST00000274008.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFG2A	ENST00000274008.5 linkuse as main transcript	c.807G>T	p.Leu269=	synonymous_variant	5/16	1	NM_145207.3	P1	Q8NB90-1

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4657

AN:

152156

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00642

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0389

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0417

Gnomad OTH

AF:

0.0210

GnomAD3 exomes

AF:

0.0341

AC:

8580

AN:

251370

Hom.:

219

AF XY:

0.0360

AC XY:

4886

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00659

Gnomad AMR exome

AF:

0.00795

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0441

Gnomad FIN exome

AF:

0.0895

Gnomad NFE exome

AF:

0.0400

Gnomad OTH exome

AF:

0.0344

GnomAD4 exome

AF:

0.0396

AC:

57822

AN:

1461884

Hom.:

1410

Cov.:

AF XY:

0.0399

AC XY:

29042

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00544

Gnomad4 AMR exome

AF:

0.00823

Gnomad4 ASJ exome

AF:

0.0156

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0465

Gnomad4 FIN exome

AF:

0.0865

Gnomad4 NFE exome

AF:

0.0415

Gnomad4 OTH exome

AF:

0.0318

GnomAD4 genome

AF:

0.0306

AC:

4657

AN:

152274

Hom.:

124

Cov.:

AF XY:

0.0329

AC XY:

2452

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00640

Gnomad4 AMR

AF:

0.0130

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0390

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.0417

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0354

Hom.:

Bravo

AF:

0.0212

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0351

EpiControl

AF:

0.0346

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 14, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 01, 2018	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 03, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.41

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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