14-24819101-C-T

Variant names:

• chr14-24819101-C-T
• rs147557535
• NM_001394410.1:c.545G>A

Variant summary

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

The NM_001394410.1(STXBP6):​c.545G>A​(p.Arg182Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: STXBP6 NM_001394410.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88
• Publications: 1 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]

ENSG00000288100 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.545G>A	p.Arg182Gln	missense	Exon 5 of 6	NP_001381339.1	Q8NFX7-1
	STXBP6	NM_001304476.3		c.545G>A	p.Arg182Gln	missense	Exon 6 of 7	NP_001291405.1	Q8NFX7-1
	STXBP6	NM_001304477.3		c.545G>A	p.Arg182Gln	missense	Exon 5 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.545G>A	p.Arg182Gln	missense	Exon 5 of 6	ENSP00000324302.5	Q8NFX7-1
	STXBP6	ENST00000396700.5	TSL:1	c.545G>A	p.Arg182Gln	missense	Exon 6 of 7	ENSP00000379928.1	Q8NFX7-1
	STXBP6	ENST00000419632.6	TSL:1	c.545G>A	p.Arg182Gln	missense	Exon 5 of 6	ENSP00000397212.2	Q8NFX7-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 250650 AF XY: 0.0000148

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1461676 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 727100

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86232

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111874

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15274

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

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	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.89	L
PhyloP100		7.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.21
Sift	Benign	0.24	T
Sift4G	Uncertain	0.038	D
Polyphen		1.0	D
Vest4		0.78
MVP		0.29
MPC		0.27
ClinPred		0.78	D
GERP RS		5.3
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.32
Mutation Taster		=71/29	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: rs147557535; hg19: chr14-25288307;