22-30285679-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001037666.3(CASTOR1):​c.931G>A​(p.Asp311Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,566,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

CASTOR1
NM_001037666.3 missense

Scores

6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48
Variant links:
Genes affected
CASTOR1 (HGNC:34423): (cytosolic arginine sensor for mTORC1 subunit 1) Enables arginine binding activity and identical protein binding activity. Involved in cellular response to L-arginine and negative regulation of TORC1 signaling. Located in cytosol. Colocalizes with GATOR2 complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.007921606).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CASTOR1NM_001037666.3 linkc.931G>A p.Asp311Asn missense_variant Exon 9 of 9 ENST00000407689.8 NP_001032755.1 Q8WTX7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CASTOR1ENST00000407689.8 linkc.931G>A p.Asp311Asn missense_variant Exon 9 of 9 1 NM_001037666.3 ENSP00000384183.4 Q8WTX7
ENSG00000248751ENST00000434291.5 linkc.1384G>A p.Asp462Asn missense_variant Exon 13 of 13 2 ENSP00000401535.1 H7C1Q1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152170
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000212
AC:
37
AN:
174656
Hom.:
0
AF XY:
0.000181
AC XY:
17
AN XY:
94090
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00126
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000644
GnomAD4 exome
AF:
0.0000290
AC:
41
AN:
1414400
Hom.:
0
Cov.:
31
AF XY:
0.0000272
AC XY:
19
AN XY:
699304
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000967
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:
9.19e-7
Gnomad4 OTH exome
AF:
0.0000513
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152170
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000422
Hom.:
0
Bravo
AF:
0.0000793
ExAC
AF:
0.000119
AC:
14

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.931G>A (p.D311N) alteration is located in exon 9 (coding exon 9) of the GATSL3 gene. This alteration results from a G to A substitution at nucleotide position 931, causing the aspartic acid (D) at amino acid position 311 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.64
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.012
T;T;.
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.0079
T;T;T
MetaSVM
Benign
-1.1
T
PROVEAN
Benign
-1.4
N;N;N
REVEL
Benign
0.066
Sift
Benign
0.034
D;D;D
Sift4G
Uncertain
0.055
T;T;D
Polyphen
0.77
P;P;.
Vest4
0.26
MutPred
0.15
Loss of helix (P = 0.1299);.;.;
MVP
0.45
MPC
0.50
ClinPred
0.064
T
GERP RS
4.1
Varity_R
0.48
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs771078179; hg19: chr22-30681668; COSMIC: COSV57575572; COSMIC: COSV57575572; API