2-213862517-T-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024532.5(SPAG16):c.1103T>A(p.Val368Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000107 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
SPAG16
NM_024532.5 missense
NM_024532.5 missense
Scores
1
11
7
Clinical Significance
Conservation
PhyloP100: 5.50
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPAG16 | NM_024532.5 | c.1103T>A | p.Val368Asp | missense_variant | 11/16 | ENST00000331683.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPAG16 | ENST00000331683.10 | c.1103T>A | p.Val368Asp | missense_variant | 11/16 | 1 | NM_024532.5 | P1 | |
SPAG16 | ENST00000406979.6 | c.*1104T>A | 3_prime_UTR_variant, NMD_transcript_variant | 13/18 | 1 | ||||
SPAG16 | ENST00000451561.1 | c.161T>A | p.Val54Asp | missense_variant | 2/6 | 3 | |||
SPAG16 | ENST00000452556.5 | c.*669T>A | 3_prime_UTR_variant, NMD_transcript_variant | 9/14 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251354Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135846
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GnomAD4 exome AF: 0.000109 AC: 160AN: 1461830Hom.: 0 Cov.: 38 AF XY: 0.000102 AC XY: 74AN XY: 727218
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74354
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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 submitter | clinical testing | Ambry Genetics | Apr 25, 2023 | The c.1103T>A (p.V368D) alteration is located in exon 11 (coding exon 11) of the SPAG16 gene. This alteration results from a T to A substitution at nucleotide position 1103, causing the valine (V) at amino acid position 368 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at