2-231000413-C-A

Variant names:

• chr2-231000413-C-A
• rs774486139
• NM_139073.5:c.349C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_139073.5(SPATA3):​c.349C>A​(p.Pro117Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,390,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P117S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: SPATA3 NM_139073.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03

Genes affected

SPATA3 (HGNC:17884): (spermatogenesis associated 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA3	NM_139073.5	c.349C>A	p.Pro117Thr	missense_variant	Exon 2 of 5	ENST00000433428.7	NP_620712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA3	ENST00000433428.7	c.349C>A	p.Pro117Thr	missense_variant	Exon 2 of 5	1	NM_139073.5	ENSP00000403804.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1390410 Hom.: 0 Cov.: 36 AF XY: 0.00000292 AC XY: 2 AN XY: 684712

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000280

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	24
DANN	Benign	0.84
DEOGEN2	Benign	0.033	.;T;T;T;.;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.80	T;.;.;.;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Pathogenic	0.78	D;D;D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.0	.;L;L;L;.;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.5	.;D;D;D;.;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.016	.;D;D;D;.;D
Sift4G	Pathogenic	0.0	.;D;D;D;D;D
Vest4		0.74, 0.77
MVP		0.11
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.27
gMVP		0.032

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: rs774486139; hg19: chr2-231865128;