2-231002760-G-C

Position:

• chr2-231002760-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_139073.5(SPATA3):​c.550G>C​(p.Gly184Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA3 NM_139073.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.244

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA3	NM_139073.5	c.550G>C	p.Gly184Arg	missense_variant	3/5	ENST00000433428.7	NP_620712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA3	ENST00000433428.7	c.550G>C	p.Gly184Arg	missense_variant	3/5	1	NM_139073.5	ENSP00000403804	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.550G>C (p.G184R) alteration is located in exon 3 (coding exon 3) of the SPATA3 gene. This alteration results from a G to C substitution at nucleotide position 550, causing the glycine (G) at amino acid position 184 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0047	.;T;T;T;.;T
Eigen	Benign	0.082
Eigen_PC	Benign	-0.0000041
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.80	T;.;.;.;T;T
M_CAP	Benign	0.0060	T
MetaRNN	Uncertain	0.47	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	.;L;L;L;.;L
MutationTaster	Benign	0.80	N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.0	.;D;D;D;.;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0040	.;D;D;D;.;D
Sift4G	Uncertain	0.0070	.;D;D;D;D;D
Vest4		0.39, 0.43
MVP		0.092
ClinPred		0.94	D
GERP RS		0.68
Varity_R		0.28
gMVP		0.0074

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-231867475;