rs1472949

chr4-123028401-G-Achr4-123028401-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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

Genes affected

SPATA5 (HGNC:):

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]

ACMG classification

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	UniProt
SPATA5	NM_145207.3	c.2079+6G>A		splice_donor_region_variant, intron_variant		ENST00000274008.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFG2A	ENST00000274008.5	c.2079+6G>A		splice_donor_region_variant, intron_variant		1	NM_145207.3	P1
AFG2A	ENST00000422835.2	n.2121+6G>A		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		1
AFG2A	ENST00000675612.1	c.2148+6G>A		splice_donor_region_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136065 AN: 152092 Hom.: 61286 Cov.: 32

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

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.: 38 AF XY: 0.943 AC XY: 685306 AN XY: 727022

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.: 32 AF XY: 0.894 AC XY: 66535 AN XY: 74410

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

Submissions by phenotype

Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Nov 04, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

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

Other links and lift over

dbSNP: rs1472949; hg19: chr4-123949556;