Variant rs1472949 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145207.3(SPATA5):c.2079+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 1,613,580 control chromosomes in the GnomAD database, including 712,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 61328 hom., cov: 32)

Exomes 𝑓: 0.94 ( 651404 hom. )

Consequence

SPATA5
NM_145207.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.00001721

Clinical Significance

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

Conservation

PhyloP100: -0.739

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 4-123028401-G-A is Benign according to our data. Variant chr4-123028401-G-A is described in ClinVar as [Benign]. Clinvar id is 203522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 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.2079+6G>A		splice_donor_region_variant, intron_variant		ENST00000274008.5	NP_660208.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
AFG2A	ENST00000274008.5 linkuse as main transcript	c.2079+6G>A	splice_donor_region_variant, intron_variant	1	NM_145207.3	ENSP00000274008	P1	Q8NB90-1
AFG2A	ENST00000422835.2 linkuse as main transcript	n.2121+6G>A	splice_donor_region_variant, intron_variant, non_coding_transcript_variant	1
AFG2A	ENST00000675612.1 linkuse as main transcript	c.2148+6G>A	splice_donor_region_variant, intron_variant			ENSP00000502453

Frequencies

GnomAD3 genomes

AF:

0.895

AC:

136065

AN:

152092

Hom.:

61286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.788

Gnomad AMI

AF:

0.998

Gnomad AMR

AF:

0.871

Gnomad ASJ

AF:

0.920

Gnomad EAS

AF:

0.959

Gnomad SAS

AF:

0.912

Gnomad FIN

AF:

0.929

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.951

Gnomad OTH

AF:

0.887

GnomAD3 exomes

AF:

0.917

AC:

230262

AN:

251028

Hom.:

105929

AF XY:

0.922

AC XY:

125069

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.790

Gnomad AMR exome

AF:

0.850

Gnomad ASJ exome

AF:

0.918

Gnomad EAS exome

AF:

0.963

Gnomad SAS exome

AF:

0.911

Gnomad FIN exome

AF:

0.927

Gnomad NFE exome

AF:

0.948

Gnomad OTH exome

AF:

0.915

GnomAD4 exome

AF:

0.943

AC:

1378684

AN:

1461370

Hom.:

651404

Cov.:

AF XY:

0.943

AC XY:

685306

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.783

Gnomad4 AMR exome

AF:

0.851

Gnomad4 ASJ exome

AF:

0.916

Gnomad4 EAS exome

AF:

0.958

Gnomad4 SAS exome

AF:

0.911

Gnomad4 FIN exome

AF:

0.930

Gnomad4 NFE exome

AF:

0.956

Gnomad4 OTH exome

AF:

0.934

GnomAD4 genome

AF:

0.895

AC:

136167

AN:

152210

Hom.:

61328

Cov.:

AF XY:

0.894

AC XY:

66535

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.788

Gnomad4 AMR

AF:

0.871

Gnomad4 ASJ

AF:

0.920

Gnomad4 EAS

AF:

0.959

Gnomad4 SAS

AF:

0.912

Gnomad4 FIN

AF:

0.929

Gnomad4 NFE

AF:

0.951

Gnomad4 OTH

AF:

0.889

Alfa

AF:

0.937

Hom.:

132666

Bravo

AF:

0.884

Asia WGS

AF:

0.937

AC:

3259

AN:

3478

EpiCase

AF:

0.950

EpiControl

AF:

0.943

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 04, 2022	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Apr 20, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.2

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.010

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