6-139242621-G-T

Variant names:

• chr6-139242621-G-T
• rs749514867
• NM_153235.4:c.1960C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153235.4(TXLNB):​c.1960C>A​(p.Pro654Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. P654S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TXLNB NM_153235.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566
• Publications: 1 publications found

Genes affected

TXLNB (HGNC:21617): (taxilin beta) Predicted to enable syntaxin binding activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293614 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07491082).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153235.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXLNB	NM_153235.4	MANE Select	c.1960C>A	p.Pro654Thr	missense	Exon 10 of 10	NP_694967.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXLNB	ENST00000358430.8	TSL:1 MANE Select	c.1960C>A	p.Pro654Thr	missense	Exon 10 of 10	ENSP00000351206.3	Q8N3L3
	ENSG00000293614	ENST00000715941.1		n.171+1974C>A		intron	N/A
	TXLNB	ENST00000715942.1		n.*607-3364C>A		intron	N/A	ENSP00000520544.1	A0ABB0MV18

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.57
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.015
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.039	D
Polyphen		0.27	B
Vest4		0.10
MutPred		0.19		Gain of phosphorylation at P654 (P = 0.0148)
MVP		0.15
MPC		0.090
ClinPred		0.38	T
GERP RS		2.9
Varity_R		0.12
gMVP		0.17
Mutation Taster		=99/1	polymorphism

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: rs749514867; hg19: chr6-139563758;