chr5-139396890-C-A

Variant names:

• chr5-139396890-C-A
• rs10900862
• NM_194296.2:c.528G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_194296.2(SPATA24):​c.528G>T​(p.Glu176Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SPATA24 NM_194296.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90
• Publications: 26 publications found

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]

ENSG00000302512 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29880795).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194296.2. 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
	SPATA24	NM_194296.2	MANE Select	c.528G>T	p.Glu176Asp	missense	Exon 6 of 6	NP_919272.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA24	ENST00000450845.7	TSL:1 MANE Select	c.528G>T	p.Glu176Asp	missense	Exon 6 of 6	ENSP00000414920.2
	SPATA24	ENST00000302091.9	TSL:2	c.554G>T	p.Arg185Ile	missense	Exon 6 of 6	ENSP00000302917.5
	SPATA24	ENST00000512761.5	TSL:5	c.372G>T	p.Glu124Asp	missense	Exon 5 of 5	ENSP00000426748.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 67

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 59700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0050	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.23
Sift	Benign	0.12	T
Sift4G	Benign	0.27	T
Polyphen		0.99	D
Vest4		0.43
MutPred		0.088		Loss of methylation at K173 (P = 0.0864)
MVP		0.030
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.26
Mutation Taster		=93/7	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10900862; hg19: chr5-138732579;