1-179917952-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015602.4(TOR1AIP1):​c.1465A>C​(p.Thr489Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. T489S) has been classified as Uncertain significance.

Frequency

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

Consequence

TOR1AIP1
NM_015602.4 missense

Scores

5
9
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.68

Publications

0 publications found
Variant links:
Genes affected
TOR1AIP1 (HGNC:29456): (torsin 1A interacting protein 1) This gene encodes a type 2 integral membrane protein that binds A- and B-type lamins. The encoded protein localizes to the inner nuclear membrane and may be involved in maintaining the attachment of the nuclear membrane to the nuclear lamina during cell division. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2016]
TOR1AIP1 Gene-Disease associations (from GenCC):
  • autosomal recessive limb-girdle muscular dystrophy type 2Y
    Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.884

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TOR1AIP1NM_015602.4 linkc.1465A>C p.Thr489Pro missense_variant Exon 10 of 10 ENST00000606911.7 NP_056417.2 Q5JTV8-1
TOR1AIP1NM_001267578.2 linkc.1468A>C p.Thr490Pro missense_variant Exon 10 of 10 NP_001254507.1 Q5JTV8-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TOR1AIP1ENST00000606911.7 linkc.1465A>C p.Thr489Pro missense_variant Exon 10 of 10 1 NM_015602.4 ENSP00000476687.1 Q5JTV8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251278
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461892
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1112010
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Uncertain
0.091
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.39
.;.;T;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.053
D
MetaRNN
Pathogenic
0.88
D;D;D;D
MetaSVM
Benign
-0.83
T
MutationAssessor
Pathogenic
3.1
.;.;M;.
PhyloP100
5.7
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-5.7
.;D;.;.
REVEL
Uncertain
0.50
Sift
Uncertain
0.0030
.;D;.;.
Sift4G
Uncertain
0.0060
D;D;D;D
Polyphen
1.0
.;.;D;.
Vest4
0.67
MutPred
0.81
.;.;Loss of catalytic residue at T489 (P = 0.0571);.;
MVP
0.60
MPC
0.59
ClinPred
0.98
D
GERP RS
3.7
Varity_R
0.96
gMVP
0.86
Mutation Taster
=51/49
polymorphism

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

Other links and lift over

dbSNP: rs375127929; hg19: chr1-179887087; API