chr1-179918249-GA-G

Variant names:

• chr1-179918249-GA-G
• rs886038426
• NM_015602.4:c.*11delA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_015602.4(TOR1AIP1):​c.*11delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,588 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TOR1AIP1 NM_015602.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.36
• 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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-179918249-GA-G is Benign according to our data. Variant chr1-179918249-GA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 257697.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1AIP1	NM_015602.4	c.*11delA		3_prime_UTR_variant	Exon 10 of 10	ENST00000606911.7	NP_056417.2
TOR1AIP1	NM_001267578.2	c.*11delA		3_prime_UTR_variant	Exon 10 of 10		NP_001254507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOR1AIP1	ENST00000606911.7	c.*11delA		3_prime_UTR_variant	Exon 10 of 10	1	NM_015602.4	ENSP00000476687.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412588 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 701082

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31294

American (AMR) AF: 0.00 AC: 0 AN: 34844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39422

South Asian (SAS) AF: 0.00 AC: 0 AN: 80226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5554

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097898

Other (OTH) AF: 0.00 AC: 0 AN: 58564

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

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: rs886038426; hg19: chr1-179887384;