rs28381989

chr4-176184858-TTCTC-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_144644.4(SPATA4):c.836_839del(p.Arg279LysfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,596,384 control chromosomes in the GnomAD database, including 11,259 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.085 (776 hom., cov: 31)
  • Exomes 𝑓: 0.11 (10483 hom.)
• Consequence: SPATA4 NM_144644.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

Genes affected

SPATA4 (HGNC:17333): (spermatogenesis associated 4) Predicted to enable microtubule binding activity. Predicted to be involved in regulation of cytoskeleton organization. Predicted to be located in cytoplasm. Predicted to be active in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA4	NM_144644.4	c.836_839del	p.Arg279LysfsTer4	frameshift_variant	6/6	ENST00000280191.7
SPATA4	XM_047449608.1	c.317_320del	p.Arg106LysfsTer4	frameshift_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA4	ENST00000280191.7	c.836_839del	p.Arg279LysfsTer4	frameshift_variant	6/6	1	NM_144644.4	P1
SPATA4	ENST00000515234.1	c.317_320del	p.Arg106LysfsTer4	frameshift_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12891 AN: 152076 Hom.: 776 Cov.: 31

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.0813

GnomAD3 exomes AF: 0.0866 AC: 20676 AN: 238762 Hom.: 1322 AF XY: 0.0870 AC XY: 11267 AN XY: 129526

Gnomad AFR exome AF: 0.0176

Gnomad AMR exome AF: 0.0345

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.000171

Gnomad SAS exome AF: 0.0308

Gnomad FIN exome AF: 0.160

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.0880

GnomAD4 exome AF: 0.113 AC: 162521 AN: 1444188 Hom.: 10483 AF XY: 0.111 AC XY: 79613 AN XY: 718350

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.0368

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.000180

Gnomad4 SAS exome AF: 0.0331

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.0971

GnomAD4 genome AF: 0.0847 AC: 12886 AN: 152196 Hom.: 776 Cov.: 31 AF XY: 0.0825 AC XY: 6139 AN XY: 74402

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.0552

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.0804

Alfa AF: 0.108 Hom.: 180

Bravo AF: 0.0741

Asia WGS AF: 0.0160 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs28381989; hg19: chr4-177106009;