NM_015602.4:c.879A>C

Variant names:

• chr1-179908645-A-C
• rs17279712
• NM_015602.4:c.879A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015602.4(TOR1AIP1):​c.879A>C​(p.Gln293His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 1,612,082 control chromosomes in the GnomAD database, including 3,475 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (320 hom., cov: 32)
  • Exomes 𝑓: 0.061 (3155 hom.)
• Consequence: TOR1AIP1 NM_015602.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0120
• Publications: 21 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002154529).
• BP6: Variant 1-179908645-A-C is Benign according to our data. Variant chr1-179908645-A-C is described in ClinVar as Benign. ClinVar VariationId is 257704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

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.879A>C	p.Gln293His	missense	Exon 8 of 10	NP_056417.2
	TOR1AIP1	NM_001267578.2		c.882A>C	p.Gln294His	missense	Exon 8 of 10	NP_001254507.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1AIP1	ENST00000606911.7	TSL:1 MANE Select	c.879A>C	p.Gln293His	missense	Exon 8 of 10	ENSP00000476687.1
	TOR1AIP1	ENST00000435319.8	TSL:1	c.516A>C	p.Gln172His	missense	Exon 8 of 10	ENSP00000393292.3
	TOR1AIP1	ENST00000271583.7	TSL:5	c.882A>C	p.Gln294His	missense	Exon 8 of 11	ENSP00000271583.3

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 8143 AN: 152174 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.0207

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0566

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0676

Gnomad OTH AF: 0.0530

GnomAD2 exomes AF: 0.0555 AC: 13934 AN: 251038 AF XY: 0.0567

Gnomad AFR exome AF: 0.0214

Gnomad AMR exome AF: 0.0439

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.00294

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.0647

Gnomad OTH exome AF: 0.0560

GnomAD4 exome AF: 0.0608 AC: 88741 AN: 1459790 Hom.: 3155 Cov.: 30 AF XY: 0.0607 AC XY: 44052 AN XY: 726314

African (AFR) AF: 0.0195 AC: 651 AN: 33458

American (AMR) AF: 0.0428 AC: 1910 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 292 AN: 26102

East Asian (EAS) AF: 0.00197 AC: 78 AN: 39650

South Asian (SAS) AF: 0.0460 AC: 3969 AN: 86192

European-Finnish (FIN) AF: 0.134 AC: 7133 AN: 53304

Middle Eastern (MID) AF: 0.0255 AC: 147 AN: 5764

European-Non Finnish (NFE) AF: 0.0642 AC: 71266 AN: 1110358

Other (OTH) AF: 0.0546 AC: 3295 AN: 60306

GnomAD4 genome AF: 0.0535 AC: 8142 AN: 152292 Hom.: 320 Cov.: 32 AF XY: 0.0555 AC XY: 4134 AN XY: 74472

African (AFR) AF: 0.0207 AC: 859 AN: 41564

American (AMR) AF: 0.0565 AC: 865 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3472

East Asian (EAS) AF: 0.00327 AC: 17 AN: 5192

South Asian (SAS) AF: 0.0398 AC: 192 AN: 4824

European-Finnish (FIN) AF: 0.135 AC: 1436 AN: 10606

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0676 AC: 4600 AN: 68016

Other (OTH) AF: 0.0520 AC: 110 AN: 2116

Alfa AF: 0.0552 Hom.: 841

Bravo AF: 0.0446

TwinsUK AF: 0.0650 AC: 241

ALSPAC AF: 0.0638 AC: 246

ESP6500AA AF: 0.0207 AC: 91

ESP6500EA AF: 0.0623 AC: 536

ExAC AF: 0.0560 AC: 6796

Asia WGS AF: 0.0270 AC: 92 AN: 3478

EpiCase AF: 0.0575

EpiControl AF: 0.0549

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.6
DANN	Benign	0.51
DEOGEN2	Benign	0.065	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.012
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.010
Sift	Benign	0.14	T
Sift4G	Benign	0.11	T
Polyphen		0.0020	B
Vest4		0.11
MutPred		0.23		Loss of MoRF binding (P = 0.0954)
MPC		0.097
ClinPred		0.0056	T
GERP RS		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.035
gMVP		0.39
Mutation Taster		=99/1	polymorphism (auto)

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: rs17279712; hg19: chr1-179877780; COSMIC: COSV54869246; COSMIC: COSV54869246;