1-32190217-A-C

Position:

• chr1-32190217-A-C

Variant summary

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

The ENST00000373610.8(TXLNA):​c.931A>C​(p.Lys311Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TXLNA ENST00000373610.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.31

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.931A>C	p.Lys311Gln	missense_variant	6/11	ENST00000373610.8	NP_787048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXLNA	ENST00000373610.8	c.931A>C	p.Lys311Gln	missense_variant	6/11	1	NM_175852.4	ENSP00000362712	P1
TXLNA	ENST00000373609.1	c.931A>C	p.Lys311Gln	missense_variant	5/10	1		ENSP00000362711	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Jan 02, 2024

The c.931A>C (p.K311Q) alteration is located in exon 6 (coding exon 5) of the TXLNA gene. This alteration results from a A to C substitution at nucleotide position 931, causing the lysine (K) at amino acid position 311 to be replaced by a glutamine (Q). 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	0.47
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.0074	T
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.21
Sift	Benign	0.043	D;D
Sift4G	Benign	0.43	T;T
Polyphen		1.0	D;D
Vest4		0.67
MutPred		0.49		Loss of ubiquitination at K311 (P = 0.0077);Loss of ubiquitination at K311 (P = 0.0077);
MVP		0.20
MPC		1.2
ClinPred		0.90	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-32655818;