rs2236358

chr1-227748061-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053052.4(SNAP47):c.325G>A(p.Val109Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 1,614,044 control chromosomes in the GnomAD database, including 6,454 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.082 (805 hom., cov: 33)
  • Exomes 𝑓: 0.065 (5649 hom.)
• Consequence: SNAP47 NM_053052.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

Genes affected

SNAP47 (HGNC:30669): (synaptosome associated protein 47) Predicted to enable SNAP receptor activity and syntaxin binding activity. Predicted to be involved in synaptic vesicle fusion to presynaptic active zone membrane and synaptic vesicle priming. Predicted to act upstream of or within long-term synaptic potentiation. Colocalizes with BLOC-1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048897266).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP47	NM_053052.4	c.325G>A	p.Val109Met	missense_variant	2/5	ENST00000617596.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP47	ENST00000617596.5	c.325G>A	p.Val109Met	missense_variant	2/5	1	NM_053052.4	P1

Frequencies

GnomAD3 genomes AF: 0.0821 AC: 12484 AN: 152112 Hom.: 803 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.0761

GnomAD3 exomes AF: 0.106 AC: 26499 AN: 251110 Hom.: 2494 AF XY: 0.0987 AC XY: 13403 AN XY: 135764

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.230

Gnomad ASJ exome AF: 0.0515

Gnomad EAS exome AF: 0.326

Gnomad SAS exome AF: 0.111

Gnomad FIN exome AF: 0.0560

Gnomad NFE exome AF: 0.0459

Gnomad OTH exome AF: 0.0680

GnomAD4 exome AF: 0.0649 AC: 94812 AN: 1461814 Hom.: 5649 Cov.: 35 AF XY: 0.0652 AC XY: 47414 AN XY: 727202

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.0487

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.0577

Gnomad4 NFE exome AF: 0.0450

Gnomad4 OTH exome AF: 0.0718

GnomAD4 genome AF: 0.0822 AC: 12510 AN: 152230 Hom.: 805 Cov.: 33 AF XY: 0.0842 AC XY: 6267 AN XY: 74438

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0586

Gnomad4 NFE AF: 0.0452

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.0594 Hom.: 1070

Bravo AF: 0.0929

TwinsUK AF: 0.0413 AC: 153

ALSPAC AF: 0.0493 AC: 190

ESP6500AA AF: 0.109 AC: 479

ESP6500EA AF: 0.0453 AC: 390

ExAC AF: 0.100 AC: 12147

Asia WGS AF: 0.203 AC: 709 AN: 3478

EpiCase AF: 0.0469

EpiControl AF: 0.0483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	14
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0012	T;T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.16	N
MetaRNN	Benign	0.0049	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L;L;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.51	N;N;.
REVEL	Benign	0.18
Sift	Benign	0.22	T;T;.
Sift4G	Benign	0.13	T;T;T
Polyphen		0.98	D;D;.
Vest4		0.024
MPC		0.14
ClinPred		0.0050	T
GERP RS		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs2236358; hg19: chr1-227935762; COSMIC: COSV59918325; COSMIC: COSV59918325;