1-32181461-A-T

Position:

• chr1-32181461-A-T

Variant summary

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

The NM_001376858.1(TXLNA):​c.-236A>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000547 in 1,461,598 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: TXLNA NM_001376858.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.30

Genes affected

TXLNA (HGNC:30685): (taxilin alpha) Predicted to enable syntaxin binding activity. Predicted to be involved in exocytosis. Predicted to act upstream of or within B cell activation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXLNA	NM_175852.4	c.389A>T	p.Asn130Ile	missense_variant	3/11	ENST00000373610.8	NP_787048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXLNA	ENST00000373610.8	c.389A>T	p.Asn130Ile	missense_variant	3/11	1	NM_175852.4	ENSP00000362712.3
TXLNA	ENST00000373609.1	c.389A>T	p.Asn130Ile	missense_variant	2/10	1		ENSP00000362711.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249706 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135158

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461598 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727066

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.389A>T (p.N130I) alteration is located in exon 3 (coding exon 2) of the TXLNA gene. This alteration results from a A to T substitution at nucleotide position 389, causing the asparagine (N) at amino acid position 130 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	.;T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.16
Sift	Uncertain	0.023	D;D
Sift4G	Benign	0.11	T;T
Polyphen		1.0	D;D
Vest4		0.65
MutPred		0.26		Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);
MVP		0.17
MPC		1.4
ClinPred		0.92	D
GERP RS		4.8
Varity_R		0.36
gMVP		0.46

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: rs149920094; hg19: chr1-32647062;