rs28381989

Variant names:

• chr4-176184858-TTCTC-T
• rs28381989
• NM_144644.4:c.836_839delGAGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_144644.4(SPATA4):​c.836_839delGAGA​(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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144644.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA4	NM_144644.4	MANE Select	c.836_839delGAGA	p.Arg279LysfsTer4	frameshift	Exon 6 of 6	NP_653245.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA4	ENST00000280191.7	TSL:1 MANE Select	c.836_839delGAGA	p.Arg279LysfsTer4	frameshift	Exon 6 of 6	ENSP00000280191.2
	SPATA4	ENST00000515234.1	TSL:1	c.317_320delGAGA	p.Arg106LysfsTer4	frameshift	Exon 5 of 5	ENSP00000422290.1

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

GnomAD2 exomes AF: 0.0866 AC: 20676 AN: 238762 AF XY: 0.0870

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 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

African (AFR) AF: 0.0150 AC: 492 AN: 32884

American (AMR) AF: 0.0368 AC: 1561 AN: 42426

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2626 AN: 25792

East Asian (EAS) AF: 0.000180 AC: 7 AN: 38966

South Asian (SAS) AF: 0.0331 AC: 2773 AN: 83858

European-Finnish (FIN) AF: 0.158 AC: 8408 AN: 53052

Middle Eastern (MID) AF: 0.0325 AC: 186 AN: 5726

European-Non Finnish (NFE) AF: 0.128 AC: 140671 AN: 1101802

Other (OTH) AF: 0.0971 AC: 5797 AN: 59682

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

African (AFR) AF: 0.0220 AC: 916 AN: 41564

American (AMR) AF: 0.0552 AC: 844 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4820

European-Finnish (FIN) AF: 0.160 AC: 1689 AN: 10574

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8636 AN: 67978

Other (OTH) AF: 0.0804 AC: 170 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=134/66	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28381989; hg19: chr4-177106009; COSMIC: COSV54570121; COSMIC: COSV54570121;