1-48298760-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_019073.4(SPATA6):c.1420T>A(p.Tyr474Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SPATA6
NM_019073.4 missense
NM_019073.4 missense
Scores
3
11
5
Clinical Significance
Conservation
PhyloP100: 6.03
Genes affected
SPATA6 (HGNC:18309): (spermatogenesis associated 6) Predicted to enable myosin light chain binding activity. Predicted to be involved in motile cilium assembly and spermatogenesis. Predicted to be located in extracellular region. Predicted to be active in sperm connecting piece. [provided by Alliance of Genome Resources, Apr 2022]
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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 |
---|---|---|---|---|---|---|---|
SPATA6 | NM_019073.4 | c.1420T>A | p.Tyr474Asn | missense_variant | 13/13 | ENST00000371847.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPATA6 | ENST00000371847.8 | c.1420T>A | p.Tyr474Asn | missense_variant | 13/13 | 1 | NM_019073.4 | P4 | |
SPATA6 | ENST00000371843.7 | c.1372T>A | p.Tyr458Asn | missense_variant | 13/13 | 1 | A1 | ||
SPATA6 | ENST00000396199.7 | c.1378T>A | p.Tyr460Asn | missense_variant | 12/12 | 2 | |||
SPATA6 | ENST00000603831.5 | c.*512T>A | 3_prime_UTR_variant, NMD_transcript_variant | 9/9 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251188Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135748
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461642Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727128
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
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 | Jan 24, 2023 | The c.1420T>A (p.Y474N) alteration is located in exon 13 (coding exon 13) of the SPATA6 gene. This alteration results from a T to A substitution at nucleotide position 1420, causing the tyrosine (Y) at amino acid position 474 to be replaced by an asparagine (N). 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
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D
REVEL
Uncertain
Sift
Pathogenic
D;.;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;D
Vest4
MutPred
Gain of loop (P = 0.0121);.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at