chr2-230996343-C-T

Position:

• chr2-230996343-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_139073.5(SPATA3):​c.110C>T​(p.Pro37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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: 0)
• Consequence: SPATA3 NM_139073.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.586

Genes affected

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

SPATA3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1662175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA3	NM_139073.5	c.110C>T	p.Pro37Leu	missense_variant	1/5	ENST00000433428.7	NP_620712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA3	ENST00000433428.7	c.110C>T	p.Pro37Leu	missense_variant	1/5	1	NM_139073.5	ENSP00000403804.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

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

Jul 17, 2024

The c.110C>T (p.P37L) alteration is located in exon 1 (coding exon 1) of the SPATA3 gene. This alteration results from a C to T substitution at nucleotide position 110, causing the proline (P) at amino acid position 37 to be replaced by a leucine (L). 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	0.093
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T;T;T;T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.50	.;.;.;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L;L;L;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.5	D;D;D;D;D
REVEL	Benign	0.071
Sift	Benign	0.13	T;T;T;T;.
Sift4G	Uncertain	0.027	D;D;D;D;T
Vest4		0.18
MutPred		0.27		Loss of relative solvent accessibility (P = 0.008);Loss of relative solvent accessibility (P = 0.008);Loss of relative solvent accessibility (P = 0.008);Loss of relative solvent accessibility (P = 0.008);.;
MVP		0.13
ClinPred		0.88	D
GERP RS		3.0
Varity_R		0.069
gMVP		0.081

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: rs1459794907; hg19: chr2-231861058;