rs1362416793

Variant names:

• chr2-231000390-A-G
• rs1362416793
• NM_139073.5:c.326A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-231000390-A-G
• chr2-231000390-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139073.5(SPATA3):​c.326A>G​(p.His109Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000728 in 1,373,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. H109L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000073 (0 hom.)
• Consequence: SPATA3 NM_139073.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027430743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA3	NM_139073.5	c.326A>G	p.His109Arg	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.326A>G	p.His109Arg	missense_variant	Exon 2 of 5	1	NM_139073.5	ENSP00000403804.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000728 AC: 10 AN: 1373460 Hom.: 0 Cov.: 36 AF XY: 0.00000593 AC XY: 4 AN XY: 674274

African (AFR) AF: 0.00 AC: 0 AN: 30906

American (AMR) AF: 0.00 AC: 0 AN: 33130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24266

East Asian (EAS) AF: 0.00 AC: 0 AN: 34776

South Asian (SAS) AF: 0.00 AC: 0 AN: 76848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.00000941 AC: 10 AN: 1062652

Other (OTH) AF: 0.00 AC: 0 AN: 56574

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.010
DANN	Benign	0.40
DEOGEN2	Benign	0.000038	.;T;T;T;.;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.34	T;.;.;.;T;T
M_CAP	Benign	0.00089	T
MetaRNN	Benign	0.027	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	.;N;N;N;.;N
PhyloP100		-1.3
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.12	.;N;N;N;.;N
REVEL	Benign	0.042
Sift	Benign	1.0	.;T;T;T;.;T
Sift4G	Benign	1.0	.;T;T;T;T;T
Vest4		0.060, 0.072
MVP		0.040
ClinPred		0.033	T
GERP RS		-8.2
Varity_R		0.023
gMVP		0.0051
Mutation Taster		=98/2	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: rs1362416793; hg19: chr2-231865105;