rs370099747

Variant names:

• chr2-231000443-G-A
• rs370099747
• NM_139073.5:c.379G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-231000443-G-A
• chr2-231000443-G-C
• chr2-231000443-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_139073.5(SPATA3):​c.379G>A​(p.Gly127Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000137 in 1,549,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G127E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: SPATA3 NM_139073.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84
• Publications: 0 publications found

Genes affected

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

SPATA3 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40065455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA3	NM_139073.5	c.379G>A	p.Gly127Arg	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.379G>A	p.Gly127Arg	missense_variant	Exon 2 of 5	1	NM_139073.5	ENSP00000403804.2

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152128 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000135 AC: 21 AN: 155484 AF XY: 0.000158

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000409

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000139 AC: 194 AN: 1397222 Hom.: 0 Cov.: 38 AF XY: 0.000151 AC XY: 104 AN XY: 688942

African (AFR) AF: 0.00 AC: 0 AN: 31540

American (AMR) AF: 0.0000563 AC: 2 AN: 35518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25138

East Asian (EAS) AF: 0.00 AC: 0 AN: 35608

South Asian (SAS) AF: 0.000430 AC: 34 AN: 79090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49238

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5692

European-Non Finnish (NFE) AF: 0.000137 AC: 148 AN: 1077478

Other (OTH) AF: 0.000155 AC: 9 AN: 57920

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152246 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74430

African (AFR) AF: 0.00 AC: 0 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.0000333 Hom.: 0

Bravo AF: 0.000117

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.000112 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.379G>A (p.G127R) alteration is located in exon 2 (coding exon 2) of the SPATA3 gene. This alteration results from a G to A substitution at nucleotide position 379, causing the glycine (G) at amino acid position 127 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	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.056	.;T;T;T;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.84	T;.;.;.;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.40	T;T;T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.0	.;L;L;L;.;L
PhyloP100		3.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.1	.;D;D;D;.;D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	.;D;D;D;.;D
Sift4G	Pathogenic	0.0	.;D;D;D;D;D
Vest4		0.90, 0.90
MVP		0.20
ClinPred		0.39	T
GERP RS		4.3
Varity_R		0.80
gMVP		0.069
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs370099747; hg19: chr2-231865158; COSMIC: COSV69202078; COSMIC: COSV69202078;