dbSNP rs1229050500: SPATA3:p.Arg15Gln (chr2-230996277-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_139073.5(SPATA3):c.44G>A(p.Arg15Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,529,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000077 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

SPATA3
NM_139073.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.766

Publications

2 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 links:

SPATA3-AS1 (HGNC:28013): (SPATA3 antisense RNA 1 (head to head))

SPATA3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.0660086).

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.44G>A	p.Arg15Gln	missense	Exon 1 of 5	NP_620712.2
	SPATA3-AS1	NR_033879.1		n.-245C>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATA3	ENST00000433428.7	TSL:1 MANE Select	c.44G>A	p.Arg15Gln	missense	Exon 1 of 5	ENSP00000403804.2	Q8NHX4
SPATA3	ENST00000424440.5	TSL:1	c.44G>A	p.Arg15Gln	missense	Exon 1 of 6	ENSP00000399514.1	Q8NHX4
SPATA3	ENST00000452881.5	TSL:2	c.44G>A	p.Arg15Gln	missense	Exon 1 of 9	ENSP00000388895.1	Q8NHX4

Frequencies

GnomAD3 genomes

AF:

0.00000772

AC:

AN:

129562

Hom.:

Cov.:

show subpopulations

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:

0.000246

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000126

AC:

AN:

158526

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000808

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000286

AC:

AN:

1400008

Hom.:

Cov.:

AF XY:

0.0000348

AC XY:

AN XY:

690484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.0000560

AC:

AN:

35710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.000168

AC:

AN:

35740

South Asian (SAS)

AF:

0.0000505

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49552

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000241

AC:

AN:

1079102

Other (OTH)

AF:

0.0000172

AC:

AN:

58192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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

AF:

0.00000772

AC:

AN:

129562

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

63536

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

34258

American (AMR)

AF:

0.00

AC:

AN:

13178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3014

East Asian (EAS)

AF:

0.00

AC:

AN:

4290

South Asian (SAS)

AF:

0.000246

AC:

AN:

4060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

58598

Other (OTH)

AF:

0.00

AC:

AN:

1688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.55

M_CAP

Benign

0.0038

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.77

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.3

REVEL

Benign

0.021

Sift

Benign

0.078

Sift4G

Benign

0.22

Vest4

0.16

MutPred

0.21

Loss of MoRF binding (P = 0.0655)

MVP

0.20

ClinPred

0.064

GERP RS

1.3

PromoterAI

-0.016

Neutral

(source)

Varity_R

0.035

gMVP

0.13

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over