14-24857064-T-G

Variant names:

• chr14-24857064-T-G
• NM_001394410.1:c.248A>C

Variant summary

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

The NM_001394410.1(STXBP6):​c.248A>C​(p.Glu83Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: STXBP6 NM_001394410.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.20
• Publications: 0 publications found

Genes affected

STXBP6 (HGNC:19666): (syntaxin binding protein 6) Enables cadherin binding activity involved in cell-cell adhesion. Predicted to be involved in Golgi to plasma membrane transport and exocytosis. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

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=0.19115019).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394410.1. 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
	STXBP6	NM_001394410.1	MANE Select	c.248A>C	p.Glu83Ala	missense	Exon 3 of 6	NP_001381339.1	Q8NFX7-1
	STXBP6	NM_001304476.3		c.248A>C	p.Glu83Ala	missense	Exon 4 of 7	NP_001291405.1	Q8NFX7-1
	STXBP6	NM_001304477.3		c.248A>C	p.Glu83Ala	missense	Exon 3 of 6	NP_001291406.1	Q8NFX7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP6	ENST00000323944.10	TSL:1 MANE Select	c.248A>C	p.Glu83Ala	missense	Exon 3 of 6	ENSP00000324302.5	Q8NFX7-1
	STXBP6	ENST00000396700.5	TSL:1	c.248A>C	p.Glu83Ala	missense	Exon 4 of 7	ENSP00000379928.1	Q8NFX7-1
	STXBP6	ENST00000419632.6	TSL:1	c.248A>C	p.Glu83Ala	missense	Exon 3 of 6	ENSP00000397212.2	Q8NFX7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460834 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726744

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111270

Other (OTH) AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 32

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	0.19
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T
Eigen	Benign	0.089
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.2
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.044
Sift	Benign	0.15	T
Sift4G	Benign	0.22	T
Polyphen		0.13	B
Vest4		0.49
MutPred		0.27		Gain of MoRF binding (P = 0.0418)
MVP		0.13
MPC		0.17
ClinPred		0.83	D
GERP RS		4.7
Varity_R		0.11
gMVP		0.25
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr14-25326270;