2-213350557-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024532.5(SPAG16):​c.674C>A​(p.Pro225Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,423,332 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P225L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SPAG16
NM_024532.5 missense

Scores

3
14
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.08
Variant links:
Genes affected
SPAG16 (HGNC:23225): (sperm associated antigen 16) Cilia and flagella are comprised of a microtubular backbone, the axoneme, which is organized by the basal body and surrounded by plasma membrane. SPAG16 encodes 2 major proteins that associate with the axoneme of sperm tail and the nucleus of postmeiotic germ cells, respectively (Zhang et al., 2007 [PubMed 17699735]).[supplied by OMIM, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPAG16NM_024532.5 linkc.674C>A p.Pro225Gln missense_variant Exon 7 of 16 ENST00000331683.10 NP_078808.3 Q8N0X2-1Q4G1A2B4DYB5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPAG16ENST00000331683.10 linkc.674C>A p.Pro225Gln missense_variant Exon 7 of 16 1 NM_024532.5 ENSP00000332592.5 Q8N0X2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.03e-7
AC:
1
AN:
1423332
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
707638
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000403
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.48
T;D;.;T
Eigen
Pathogenic
0.68
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Uncertain
0.087
D
MetaRNN
Uncertain
0.74
D;D;D;D
MetaSVM
Uncertain
0.059
D
MutationAssessor
Pathogenic
2.9
.;M;.;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-6.6
D;D;D;D
REVEL
Uncertain
0.37
Sift
Uncertain
0.0040
D;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.75, 0.74, 0.78
MutPred
0.53
Gain of MoRF binding (P = 0.1416);Gain of MoRF binding (P = 0.1416);.;Gain of MoRF binding (P = 0.1416);
MVP
0.85
MPC
0.17
ClinPred
0.99
D
GERP RS
4.6
Varity_R
0.62
gMVP
0.075

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-214215281; COSMIC: COSV55983306; API