5-139396890-C-T

Position:

• chr5-139396890-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194296.2(SPATA24):​c.528G>A​(p.Glu176Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.624 in 1,551,496 control chromosomes in the GnomAD database, including 314,613 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (22364 hom., cov: 32)
  • Exomes 𝑓: 0.64 (292249 hom.)
• Consequence: SPATA24 NM_194296.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90

Genes affected

SPATA24 (HGNC:27322): (spermatogenesis associated 24) Predicted to enable DNA binding activity and identical protein binding activity. Predicted to be involved in cell differentiation and spermatogenesis. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.923242E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA24	NM_194296.2	c.528G>A	p.Glu176Glu	synonymous_variant	6/6	ENST00000450845.7	NP_919272.1
SPATA24	XM_005271916.5	c.554G>A	p.Arg185Lys	missense_variant	6/6		XP_005271973.1
SPATA24	XM_011543252.3	c.437G>A	p.Arg146Lys	missense_variant	6/6		XP_011541554.1
SPATA24	XM_011543253.3	c.437G>A	p.Arg146Lys	missense_variant	6/6		XP_011541555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA24	ENST00000450845.7	c.528G>A	p.Glu176Glu	synonymous_variant	6/6	1	NM_194296.2	ENSP00000414920.2
SPATA24	ENST00000302091.9	c.554G>A	p.Arg185Lys	missense_variant	6/6	2		ENSP00000302917.5
SPATA24	ENST00000514983.5	c.413G>A	p.Arg138Lys	missense_variant	5/5	5		ENSP00000423424.1
SPATA24	ENST00000512761.5	c.372G>A	p.Glu124Glu	synonymous_variant	5/5	5		ENSP00000426748.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75531 AN: 151992 Hom.: 22372 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.510

GnomAD3 exomes AF: 0.584 AC: 91392 AN: 156548 Hom.: 28235 AF XY: 0.586 AC XY: 48659 AN XY: 82970

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.624

Gnomad ASJ exome AF: 0.537

Gnomad EAS exome AF: 0.297

Gnomad SAS exome AF: 0.553

Gnomad FIN exome AF: 0.700

Gnomad NFE exome AF: 0.660

Gnomad OTH exome AF: 0.585

GnomAD4 exome AF: 0.638 AC: 892645 AN: 1399384 Hom.: 292249 Cov.: 67 AF XY: 0.637 AC XY: 439555 AN XY: 690200

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.553

Gnomad4 FIN exome AF: 0.690

Gnomad4 NFE exome AF: 0.672

Gnomad4 OTH exome AF: 0.581

GnomAD4 genome AF: 0.496 AC: 75523 AN: 152112 Hom.: 22364 Cov.: 32 AF XY: 0.496 AC XY: 36854 AN XY: 74362

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.506

Alfa AF: 0.616 Hom.: 47876

Bravo AF: 0.474

TwinsUK AF: 0.655 AC: 2428

ALSPAC AF: 0.667 AC: 2569

ESP6500AA AF: 0.169 AC: 234

ESP6500EA AF: 0.650 AC: 2067

ExAC AF: 0.526 AC: 12915

Asia WGS AF: 0.398 AC: 1383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	0.060
CADD	Benign	9.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0040	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0000099	T
MetaSVM	Benign	-0.91	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.21
Sift	Benign	0.14	T
Polyphen		1.0	D
ClinPred		0.034	T
GERP RS		5.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10900862; hg19: chr5-138732579; COSMIC: COSV57474341; COSMIC: COSV57474341;