2-231000413-C-T

Variant names:

• chr2-231000413-C-T
• rs774486139
• NM_139073.5:c.349C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_139073.5(SPATA3):​c.349C>T​(p.Pro117Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000908 in 1,542,594 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000098 (0 hom.)
• Consequence: SPATA3 NM_139073.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03
• 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 0 ACMG points.

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.349C>T	p.Pro117Ser	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.349C>T	p.Pro117Ser	missense	Exon 2 of 5	ENSP00000403804.2	Q8NHX4
	SPATA3	ENST00000424440.5	TSL:1	c.349C>T	p.Pro117Ser	missense	Exon 2 of 6	ENSP00000399514.1	Q8NHX4
	SPATA3	ENST00000645363.1		c.838C>T	p.Pro280Ser	missense	Exon 2 of 3	ENSP00000494655.1	A0A2R8Y5R0

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152186 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000328 AC: 5 AN: 152568 AF XY: 0.0000371

Gnomad AFR exome AF: 0.000128

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: 0.0000680

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000978 AC: 136 AN: 1390408 Hom.: 0 Cov.: 36 AF XY: 0.000102 AC XY: 70 AN XY: 684710

African (AFR) AF: 0.00 AC: 0 AN: 31374

American (AMR) AF: 0.0000286 AC: 1 AN: 34956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24934

East Asian (EAS) AF: 0.00 AC: 0 AN: 35346

South Asian (SAS) AF: 0.00 AC: 0 AN: 78566

European-Finnish (FIN) AF: 0.0000204 AC: 1 AN: 49070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.000123 AC: 132 AN: 1072996

Other (OTH) AF: 0.0000348 AC: 2 AN: 57498

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152186 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000677 Hom.: 0

Bravo AF: 0.0000227

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000109 AC: 3

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	Uncertain	0.39
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	24
DANN	Benign	0.88
DEOGEN2	Benign	0.033	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0081	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.22
Sift	Benign	0.033	D
Sift4G	Pathogenic	0.0	D
Vest4		0.62
MVP		0.12
ClinPred		0.64	D
GERP RS		4.3
Varity_R		0.19
gMVP		0.033
Mutation Taster		=89/11	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: rs774486139; hg19: chr2-231865128; COSMIC: COSV105343293; COSMIC: COSV105343293;