chr1-48359748-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019073.4(SPATA6):​c.932G>T​(p.Arg311Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R311K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SPATA6
NM_019073.4 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.00
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2428836).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPATA6NM_019073.4 linkc.932G>T p.Arg311Ile missense_variant Exon 10 of 13 ENST00000371847.8 NP_061946.1 Q9NWH7-1A0A140VJV1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPATA6ENST00000371847.8 linkc.932G>T p.Arg311Ile missense_variant Exon 10 of 13 1 NM_019073.4 ENSP00000360913.3 Q9NWH7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460532
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726548
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:
0.00
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
Benign
0.15
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.017
T;T;.;.
Eigen
Benign
-0.11
Eigen_PC
Benign
0.024
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.88
D;D;D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.24
T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.46
N;.;N;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-2.2
N;.;N;D
REVEL
Benign
0.11
Sift
Uncertain
0.0020
D;.;D;D
Sift4G
Uncertain
0.0090
D;D;D;.
Polyphen
0.0050
B;.;B;.
Vest4
0.22
MutPred
0.63
Loss of disorder (P = 0.0382);.;Loss of disorder (P = 0.0382);.;
MVP
0.18
MPC
0.44
ClinPred
0.59
D
GERP RS
4.3
Varity_R
0.12
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: chr1-48825420; API