16-89658260-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001271907.2(SPATA33):ā€‹c.50A>Gā€‹(p.Lys17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000016 ( 0 hom. )

Consequence

SPATA33
NM_001271907.2 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.797
Variant links:
Genes affected
SPATA33 (HGNC:26463): (spermatogenesis associated 33) Predicted to act upstream of or within cellular protein localization; fertilization; and flagellated sperm motility. Predicted to be located in sperm mitochondrial sheath. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.055540234).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPATA33NM_001271907.2 linkuse as main transcriptc.50A>G p.Lys17Arg missense_variant 2/3 ENST00000579310.6 NP_001258836.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPATA33ENST00000579310.6 linkuse as main transcriptc.50A>G p.Lys17Arg missense_variant 2/32 NM_001271907.2 ENSP00000462996 P2Q96N06-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152258
Hom.:
0
Cov.:
32
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251244
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135870
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461812
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152258
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000302
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 30, 2023The c.47A>G (p.K16R) alteration is located in exon 2 (coding exon 2) of the SPATA33 gene. This alteration results from a A to G substitution at nucleotide position 47, causing the lysine (K) at amino acid position 16 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
14
DANN
Benign
0.80
DEOGEN2
Benign
0.0068
T;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.36
T;T;T
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.056
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.97
L;.;.
MutationTaster
Benign
1.0
N;N;N
PROVEAN
Benign
-1.3
N;.;.
REVEL
Benign
0.014
Sift
Pathogenic
0.0
D;.;.
Sift4G
Benign
0.36
T;T;T
Polyphen
0.093
B;.;.
Vest4
0.10
MVP
0.030
MPC
0.033
ClinPred
0.23
T
GERP RS
-0.89
Varity_R
0.13
gMVP
0.0054

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370564618; hg19: chr16-89724668; API