chr7-135240621-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001394401.1(STRA8):c.97C>T(p.Arg33Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000465 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000048 ( 0 hom. )
Consequence
STRA8
NM_001394401.1 missense
NM_001394401.1 missense
Scores
9
8
2
Clinical Significance
Conservation
PhyloP100: 5.35
Genes affected
STRA8 (HGNC:30653): (stimulated by retinoic acid 8) This gene encodes a retinoic acid-responsive protein. A homologous protein in mouse has been shown to be involved in the regulation of meiotic initiation in both spermatogenesis and oogenesis, though feature differences between the mouse and human proteins suggest that these homologs are not entirely functionally equivalent. It is thought that this gene may play a role in spermatogenesis in humans. [provided by RefSeq, Nov 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.744
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STRA8 | NM_001394401.1 | c.97C>T | p.Arg33Trp | missense_variant | 2/9 | ENST00000662584.2 | |
STRA8 | NM_182489.3 | c.97C>T | p.Arg33Trp | missense_variant | 2/9 | ||
STRA8 | XM_011516137.3 | c.97C>T | p.Arg33Trp | missense_variant | 1/8 | ||
STRA8 | XM_047420324.1 | c.97C>T | p.Arg33Trp | missense_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STRA8 | ENST00000662584.2 | c.97C>T | p.Arg33Trp | missense_variant | 2/9 | NM_001394401.1 | P2 | ||
STRA8 | ENST00000275764.3 | c.163C>T | p.Arg55Trp | missense_variant | 2/9 | 1 | A2 | ||
STRA8 | ENST00000667288.1 | c.97C>T | p.Arg33Trp | missense_variant | 2/9 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
5
AN:
152198
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 251030Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135842
GnomAD3 exomes
AF:
AC:
3
AN:
251030
Hom.:
AF XY:
AC XY:
3
AN XY:
135842
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461828Hom.: 0 Cov.: 35 AF XY: 0.0000564 AC XY: 41AN XY: 727210
GnomAD4 exome
AF:
AC:
70
AN:
1461828
Hom.:
Cov.:
35
AF XY:
AC XY:
41
AN XY:
727210
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74344
GnomAD4 genome
?
AF:
AC:
5
AN:
152198
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74344
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
2
ALSPAC
AF:
AC:
0
ExAC
?
AF:
AC:
3
EpiCase
AF:
EpiControl
AF:
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 | Jul 05, 2023 | The c.163C>T (p.R55W) alteration is located in exon 2 (coding exon 2) of the STRA8 gene. This alteration results from a C to T substitution at nucleotide position 163, causing the arginine (R) at amino acid position 55 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of disorder (P = 0.0083);
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