rs140608295

Variant summary

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

The NM_174927.3(SPATA19):​c.446G>T​(p.Arg149Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R149H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SPATA19
NM_174927.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.216
Variant links:
Genes affected
SPATA19 (HGNC:30614): (spermatogenesis associated 19) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in mitochondrial outer membrane. [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 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
SPATA19NM_174927.3 linkc.446G>T p.Arg149Leu missense_variant Exon 6 of 7 ENST00000299140.8 NP_777587.1 Q7Z5L4A0A140VKB6
SPATA19NM_001291992.2 linkc.446G>T p.Arg149Leu missense_variant Exon 6 of 7 NP_001278921.1 Q7Z5L4A0A140VKB6
SPATA19XR_947806.2 linkn.513G>T non_coding_transcript_exon_variant Exon 6 of 8
SPATA19XR_947807.2 linkn.513G>T non_coding_transcript_exon_variant Exon 6 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPATA19ENST00000299140.8 linkc.446G>T p.Arg149Leu missense_variant Exon 6 of 7 1 NM_174927.3 ENSP00000299140.3 Q7Z5L4
SPATA19ENST00000532889.1 linkc.446G>T p.Arg149Leu missense_variant Exon 6 of 7 5 ENSP00000435248.1 Q7Z5L4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461700
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727128
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.084
T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.025
N
LIST_S2
Benign
0.53
.;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N;N
PrimateAI
Benign
0.19
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Benign
0.046
Sift
Benign
0.074
T;T
Sift4G
Benign
0.13
T;T
Polyphen
0.26
B;B
Vest4
0.23
MutPred
0.24
Loss of MoRF binding (P = 0.0028);Loss of MoRF binding (P = 0.0028);
MVP
0.15
MPC
0.062
ClinPred
0.11
T
GERP RS
3.2
Varity_R
0.074
gMVP
0.021

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.27
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.27
Position offset: -9

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: chr11-133711992; API