chr1-179882527-G-C

Variant names:

• chr1-179882527-G-C
• rs1647735595
• NM_015602.4:c.25G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015602.4(TOR1AIP1):​c.25G>C​(p.Glu9Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,312,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. E9K) 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: 2.65

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]

ENSG00000272906 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20333153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1AIP1	NM_015602.4	c.25G>C	p.Glu9Gln	missense_variant	Exon 1 of 10	ENST00000606911.7	NP_056417.2
TOR1AIP1	NM_001267578.2	c.25G>C	p.Glu9Gln	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.25G>C	p.Glu9Gln	missense_variant	Exon 1 of 10	1	NM_015602.4	ENSP00000476687.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1312182 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 638406

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000192

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.075	.;.;T
Eigen	Benign	-0.013
Eigen_PC	Benign	0.086
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.90	N;N;.
REVEL	Benign	0.045
Sift	Benign	0.17	T;T;.
Sift4G	Benign	0.11	T;T;T
Polyphen		0.18	.;.;B
Vest4		0.14
MutPred		0.23		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.68
MPC		0.51
ClinPred		0.84	D
GERP RS		5.3
Varity_R		0.17
gMVP		0.19

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: rs1647735595; hg19: chr1-179851662;