chr2-231000482-C-T

Variant names:

• chr2-231000482-C-T
• rs1196954034
• NM_139073.5:c.418C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_139073.5(SPATA3):​c.418C>T​(p.Arg140Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,397,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. R140Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SPATA3 NM_139073.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.540
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30521).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139073.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA3	NM_139073.5	MANE Select	c.418C>T	p.Arg140Trp	missense	Exon 2 of 5	NP_620712.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA3	ENST00000433428.7	TSL:1 MANE Select	c.418C>T	p.Arg140Trp	missense	Exon 2 of 5	ENSP00000403804.2	Q8NHX4
	SPATA3	ENST00000424440.5	TSL:1	c.418C>T	p.Arg140Trp	missense	Exon 2 of 6	ENSP00000399514.1	Q8NHX4
	SPATA3	ENST00000645363.1		c.907C>T	p.Arg303Trp	missense	Exon 2 of 3	ENSP00000494655.1	A0A2R8Y5R0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000192 AC: 3 AN: 156094 AF XY: 0.0000363

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000497

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000143 AC: 20 AN: 1397454 Hom.: 0 Cov.: 38 AF XY: 0.0000189 AC XY: 13 AN XY: 688962

African (AFR) AF: 0.00 AC: 0 AN: 31554

American (AMR) AF: 0.00 AC: 0 AN: 35552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25144

East Asian (EAS) AF: 0.00 AC: 0 AN: 35668

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79120

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.0000148 AC: 16 AN: 1077538

Other (OTH) AF: 0.0000345 AC: 2 AN: 57904

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.54
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.19
Sift	Benign	0.041	D
Sift4G	Pathogenic	0.0	D
Vest4		0.43
MVP		0.17
ClinPred		0.69	D
GERP RS		3.2
Varity_R		0.13
gMVP		0.026
Mutation Taster		=95/5	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: rs1196954034; hg19: chr2-231865197; COSMIC: COSV105343296; COSMIC: COSV105343296;