rs627897

chr1-179917990-G-Achr1-179917990-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015602.4(TOR1AIP1):c.1503G>A(p.Ala501=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 1,614,166 control chromosomes in the GnomAD database, including 728,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66292 hom., cov: 33)
  • Exomes 𝑓: 0.95 (662548 hom.)
• Consequence: TOR1AIP1 NM_015602.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0140

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-179917990-G-A is Benign according to our data. Variant chr1-179917990-G-A is described in ClinVar as [Benign]. Clinvar id is 257698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-179917990-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.014 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOR1AIP1	NM_015602.4	c.1503G>A	p.Ala501=	synonymous_variant	10/10	ENST00000606911.7
TOR1AIP1	NM_001267578.2	c.1506G>A	p.Ala502=	synonymous_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOR1AIP1	ENST00000606911.7	c.1503G>A	p.Ala501=	synonymous_variant	10/10	1	NM_015602.4	P4

Frequencies

GnomAD3 genomes AF: 0.932 AC: 141871 AN: 152154 Hom.: 66244 Cov.: 33

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.981

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.928

GnomAD3 exomes AF: 0.950 AC: 238682 AN: 251342 Hom.: 113448 AF XY: 0.951 AC XY: 129221 AN XY: 135840

Gnomad AFR exome AF: 0.875

Gnomad AMR exome AF: 0.962

Gnomad ASJ exome AF: 0.957

Gnomad EAS exome AF: 0.900

Gnomad SAS exome AF: 0.957

Gnomad FIN exome AF: 0.979

Gnomad NFE exome AF: 0.956

Gnomad OTH exome AF: 0.956

GnomAD4 exome AF: 0.952 AC: 1391452 AN: 1461894 Hom.: 662548 Cov.: 82 AF XY: 0.952 AC XY: 692399 AN XY: 727248

Gnomad4 AFR exome AF: 0.869

Gnomad4 AMR exome AF: 0.961

Gnomad4 ASJ exome AF: 0.957

Gnomad4 EAS exome AF: 0.900

Gnomad4 SAS exome AF: 0.956

Gnomad4 FIN exome AF: 0.979

Gnomad4 NFE exome AF: 0.954

Gnomad4 OTH exome AF: 0.948

GnomAD4 genome AF: 0.932 AC: 141977 AN: 152272 Hom.: 66292 Cov.: 33 AF XY: 0.933 AC XY: 69488 AN XY: 74460

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.954

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.981

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.929

Alfa AF: 0.948 Hom.: 55968

Bravo AF: 0.926

Asia WGS AF: 0.931 AC: 3238 AN: 3478

EpiCase AF: 0.952

EpiControl AF: 0.955

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2Y Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	8.7
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs627897; hg19: chr1-179887125;