Variant rs6534369 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_145207.3(SPATA5):c.1527C>T(p.Leu509=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,613,388 control chromosomes in the GnomAD database, including 1,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 522 hom., cov: 32)

Exomes 𝑓: 0.018 ( 739 hom. )

Consequence

SPATA5
NM_145207.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0470

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 4-122947301-C-T is Benign according to our data. Variant chr4-122947301-C-T is described in ClinVar as [Benign]. Clinvar id is 448460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.047 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA5	NM_145207.3 linkuse as main transcript	c.1527C>T	p.Leu509=	synonymous_variant	9/16	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.1527C>T	p.Leu509=	synonymous_variant	9/16	1	NM_145207.3	ENSP00000274008	P1	Q8NB90-1
AFG2A	ENST00000422835.2 linkuse as main transcript	n.1569C>T		non_coding_transcript_exon_variant	9/15	1
AFG2A	ENST00000675612.1 linkuse as main transcript	c.1524C>T	p.Leu508=	synonymous_variant	9/17			ENSP00000502453
AFG2A	ENST00000674886.1 linkuse as main transcript	n.1589C>T		non_coding_transcript_exon_variant	9/11

Frequencies

GnomAD3 genomes

AF:

0.0534

AC:

8111

AN:

152008

Hom.:

520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0148

Gnomad OTH

AF:

0.0454

GnomAD3 exomes

AF:

0.0210

AC:

5259

AN:

251000

Hom.:

256

AF XY:

0.0182

AC XY:

2471

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.0235

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.00407

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.0170

GnomAD4 exome

AF:

0.0180

AC:

26365

AN:

1461264

Hom.:

739

Cov.:

AF XY:

0.0168

AC XY:

12223

AN XY:

726934

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.0162

Gnomad4 ASJ exome

AF:

0.0251

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00132

Gnomad4 FIN exome

AF:

0.00487

Gnomad4 NFE exome

AF:

0.0158

Gnomad4 OTH exome

AF:

0.0234

GnomAD4 genome

AF:

0.0534

AC:

8127

AN:

152124

Hom.:

522

Cov.:

AF XY:

0.0522

AC XY:

3879

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.0283

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.0148

Gnomad4 OTH

AF:

0.0449

Alfa

AF:

0.0216

Hom.:

239

Bravo

AF:

0.0612

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0152

EpiControl

AF:

0.0153

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jun 26, 2017

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

5.8

DANN

Benign

0.73

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over