1-179882573-C-T

Variant names:

• chr1-179882573-C-T
• rs1553240696
• NM_015602.4:c.71C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015602.4(TOR1AIP1):​c.71C>T​(p.Pro24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P24A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TOR1AIP1 NM_015602.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35
• Publications: 0 publications found

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)

ENSG00000272906 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
TOR1AIP1	NM_015602.4	c.71C>T	p.Pro24Leu	missense_variant	Exon 1 of 10	ENST00000606911.7	NP_056417.2
TOR1AIP1	NM_001267578.2	c.71C>T	p.Pro24Leu	missense_variant	Exon 1 of 10		NP_001254507.1
LOC139427322	NM_001436163.1	c.*180C>T		downstream_gene_variant			NP_001423092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOR1AIP1	ENST00000606911.7	c.71C>T	p.Pro24Leu	missense_variant	Exon 1 of 10	1	NM_015602.4	ENSP00000476687.1
ENSG00000293564	ENST00000713864.1	c.*180C>T		downstream_gene_variant				ENSP00000519169.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	.;.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	2.0	M;.;M
PhyloP100		3.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.9	D;D;.
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.74
MutPred		0.41		Loss of disorder (P = 0.0155);Loss of disorder (P = 0.0155);Loss of disorder (P = 0.0155);
MVP		0.72
MPC		0.52
ClinPred		0.99	D
GERP RS		4.4
PromoterAI		0.058	Neutral
Varity_R		0.54
gMVP		0.25
Mutation Taster		=88/12	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

Other links and lift over

dbSNP: rs1553240696; hg19: chr1-179851708;