dbSNP rs764212802: SPATA3:p.Ala145Glu (chr2-231000498-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139073.5(SPATA3):c.434C>A(p.Ala145Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,338 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. A145V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SPATA3
NM_139073.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

0 publications found

Variant links:

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

SPATA3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09792191).

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.434C>A	p.Ala145Glu	missense	Exon 2 of 5	NP_620712.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATA3	ENST00000433428.7	TSL:1 MANE Select	c.434C>A	p.Ala145Glu	missense	Exon 2 of 5	ENSP00000403804.2	Q8NHX4
SPATA3	ENST00000424440.5	TSL:1	c.434C>A	p.Ala145Glu	missense	Exon 2 of 6	ENSP00000399514.1	Q8NHX4
SPATA3	ENST00000645363.1		c.923C>A	p.Ala308Glu	missense	Exon 2 of 3	ENSP00000494655.1	A0A2R8Y5R0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1395338

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687762

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31504

American (AMR)

AF:

0.00

AC:

AN:

35348

Ashkenazi Jewish (ASJ)

AF:

0.0000399

AC:

AN:

25038

East Asian (EAS)

AF:

0.00

AC:

AN:

35590

South Asian (SAS)

AF:

0.00

AC:

AN:

78882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076302

Other (OTH)

AF:

0.00

AC:

AN:

57818

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0023

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.52

M_CAP

Benign

0.0043

MetaRNN

Benign

0.098

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.1

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.83

REVEL

Benign

0.082

Sift

Benign

0.038

Sift4G

Uncertain

0.037

Vest4

0.40

MVP

0.040

ClinPred

0.46

GERP RS

3.0

Varity_R

0.061

gMVP

0.022

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over