TOR1AIP1 p.Arg192Arg

Variant names:

• chr1-179889332-C-C
• ENST00000606911.7:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-179889333--
• chr1-179889333-A-C
• chr1-179889335-G-A
• chr1-179889333-AGG-CGT
• chr1-179889333-AGG-CGC
• chr1-179889333-AGG-CGA

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The ENST00000606911.7(TOR1AIP1):​c. variant causes a splice donor, intron 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TOR1AIP1 ENST00000606911.7 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• 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):

• TOR1AIP1-related multisystem disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• TOR1AIP1-related myopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2Y

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.032534245 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000606911.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1AIP1	ENST00000606911.7	TSL:1 MANE Select	c.		splice_donor intron	N/A	ENSP00000476687.1	Q5JTV8-1
	TOR1AIP1	ENST00000435319.8	TSL:1	c.		splice_donor intron	N/A	ENSP00000393292.3	Q5JTV8-4
	TOR1AIP1	ENST00000271583.7	TSL:5	c.		splice_donor intron	N/A	ENSP00000271583.3	J3KN66

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.077

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-179858467;