chr6-139242537-C-T

Variant names:

• chr6-139242537-C-T
• rs748452707
• NM_153235.4:c.2044G>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.2044G>A​(p.Gly682Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000999 in 1,502,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G682R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: TXLNB NM_153235.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.875
• Publications: 0 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=0.17908582).

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.2044G>A	p.Gly682Ser	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.2044G>A	p.Gly682Ser	missense	Exon 10 of 10	ENSP00000351206.3	Q8N3L3
	ENSG00000293614	ENST00000715941.1		n.171+2058G>A		intron	N/A
	TXLNB	ENST00000715942.1		n.*607-3280G>A		intron	N/A	ENSP00000520544.1	A0ABB0MV18

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152262 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 168388 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000104 AC: 14 AN: 1349806 Hom.: 0 Cov.: 30 AF XY: 0.0000106 AC XY: 7 AN XY: 660274

African (AFR) AF: 0.00 AC: 0 AN: 29344

American (AMR) AF: 0.00 AC: 0 AN: 26952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19554

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37518

South Asian (SAS) AF: 0.00 AC: 0 AN: 68430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3644

European-Non Finnish (NFE) AF: 0.0000123 AC: 13 AN: 1059420

Other (OTH) AF: 0.00 AC: 0 AN: 55290

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152262 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74396

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.88
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.041
Sift	Uncertain	0.013	D
Sift4G	Benign	0.17	T
Polyphen		0.96	D
Vest4		0.18
MutPred		0.16		Gain of phosphorylation at G682 (P = 0.099)
MVP		0.37
MPC		0.24
ClinPred		0.44	T
GERP RS		3.5
Varity_R		0.059
gMVP		0.077
Mutation Taster		=98/2	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: rs748452707; hg19: chr6-139563674;