1-179882939-T-G

Variant names:

• chr1-179882939-T-G
• rs1281378
• NM_015602.4:c.437T>G

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.437T>G​(p.Met146Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. M146T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOR1AIP1 NM_015602.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• Publications: 40 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=0.08147952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1AIP1	NM_015602.4	c.437T>G	p.Met146Arg	missense_variant	Exon 1 of 10	ENST00000606911.7	NP_056417.2
TOR1AIP1	NM_001267578.2	c.437T>G	p.Met146Arg	missense_variant	Exon 1 of 10		NP_001254507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOR1AIP1	ENST00000606911.7	c.437T>G	p.Met146Arg	missense_variant	Exon 1 of 10	1	NM_015602.4	ENSP00000476687.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.73
DEOGEN2	Benign	0.0	.;.;T;.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.78	T;T;T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.081	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.;L;.;.
PhyloP100		0.48
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.66	N;N;.;.;N
REVEL	Benign	0.011
Sift	Uncertain	0.0030	D;D;.;.;D
Sift4G	Benign	0.35	T;T;T;T;D
Vest4		0.27
ClinPred		0.21	T
GERP RS		-1.5
PromoterAI		0.047	Neutral
Varity_R		0.80
gMVP		0.073
Mutation Taster		=98/2	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: rs1281378; hg19: chr1-179852074;