NM_024532.5:c.170A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024532.5(SPAG16):​c.170A>C​(p.Tyr57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. Y57C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

SPAG16
NM_024532.5 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.65
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32138234).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPAG16NM_024532.5 linkc.170A>C p.Tyr57Ser missense_variant Exon 2 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.170A>C p.Tyr57Ser missense_variant Exon 2 of 16 1 NM_024532.5 ENSP00000332592.5 Q8N0X2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455010
Hom.:
0
Cov.:
27
AF XY:
0.00000138
AC XY:
1
AN XY:
724230
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:
9.04e-7
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
Benign
0.12
BayesDel_addAF
Benign
-0.056
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.12
T;T;.;T
Eigen
Benign
-0.085
Eigen_PC
Benign
-0.081
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.76
T;T;T;T
M_CAP
Benign
0.042
D
MetaRNN
Benign
0.32
T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.7
.;L;L;.
PrimateAI
Benign
0.42
T
PROVEAN
Pathogenic
-4.8
D;D;D;D
REVEL
Benign
0.13
Sift
Benign
0.098
T;D;D;T
Sift4G
Uncertain
0.010
D;D;D;D
Polyphen
0.84, 0.74, 0.94
.;P;P;P
Vest4
0.62, 0.66, 0.67
MutPred
0.46
Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);
MVP
0.65
MPC
0.073
ClinPred
0.92
D
GERP RS
1.5
Varity_R
0.22
gMVP
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr2-214160821; API