1-179882539-G-C

Variant names:

• chr1-179882539-G-C
• rs749592068
• NM_015602.4:c.37G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015602.4(TOR1AIP1):​c.37G>C​(p.Glu13Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000151 in 1,327,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. E13K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: TOR1AIP1 NM_015602.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24055284).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015602.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1AIP1	NM_015602.4	MANE Select	c.37G>C	p.Glu13Gln	missense	Exon 1 of 10	NP_056417.2
	TOR1AIP1	NM_001267578.2		c.37G>C	p.Glu13Gln	missense	Exon 1 of 10	NP_001254507.1
	LOC139427322	NM_001436163.1		c.*146G>C		downstream_gene	N/A	NP_001423092.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1AIP1	ENST00000606911.7	TSL:1 MANE Select	c.37G>C	p.Glu13Gln	missense	Exon 1 of 10	ENSP00000476687.1
	TOR1AIP1	ENST00000271583.7	TSL:5	c.37G>C	p.Glu13Gln	missense	Exon 1 of 11	ENSP00000271583.3
	TOR1AIP1	ENST00000528443.6	TSL:2	c.37G>C	p.Glu13Gln	missense	Exon 1 of 10	ENSP00000435365.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000151 AC: 2 AN: 1327830 Hom.: 0 Cov.: 29 AF XY: 0.00000154 AC XY: 1 AN XY: 647868

African (AFR) AF: 0.00 AC: 0 AN: 29158

American (AMR) AF: 0.00 AC: 0 AN: 22920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19088

East Asian (EAS) AF: 0.00 AC: 0 AN: 36172

South Asian (SAS) AF: 0.00 AC: 0 AN: 65686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5104

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1049050

Other (OTH) AF: 0.00 AC: 0 AN: 54638

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.083
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.14
Sift	Uncertain	0.017	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.17
MutPred		0.28		Loss of catalytic residue at W15 (P = 0.0598)
MVP		0.55
MPC		0.46
ClinPred		0.88	D
GERP RS		5.3
PromoterAI		-0.038	Neutral
Varity_R		0.10
gMVP		0.16
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749592068; hg19: chr1-179851674;