chr1-227748061-G-A

Variant names:

• chr1-227748061-G-A
• rs2236358
• NM_053052.4:c.325G>A

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SNAP47	NM_053052.4	c.325G>A	p.Val109Met	missense_variant	Exon 2 of 5	ENST00000617596.5	NP_444280.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP47	ENST00000617596.5	c.325G>A	p.Val109Met	missense_variant	Exon 2 of 5	1	NM_053052.4	ENSP00000483253.1

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

GnomAD2 exomes AF: 0.106 AC: 26499 AN: 251110 AF XY: 0.0987

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 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

African (AFR) AF: 0.109 AC: 3639 AN: 33480

American (AMR) AF: 0.214 AC: 9552 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 1274 AN: 26134

East Asian (EAS) AF: 0.323 AC: 12838 AN: 39700

South Asian (SAS) AF: 0.111 AC: 9582 AN: 86242

European-Finnish (FIN) AF: 0.0577 AC: 3079 AN: 53390

Middle Eastern (MID) AF: 0.0844 AC: 487 AN: 5768

European-Non Finnish (NFE) AF: 0.0450 AC: 50026 AN: 1111982

Other (OTH) AF: 0.0718 AC: 4335 AN: 60396

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

African (AFR) AF: 0.103 AC: 4296 AN: 41536

American (AMR) AF: 0.124 AC: 1893 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.331 AC: 1704 AN: 5154

South Asian (SAS) AF: 0.118 AC: 570 AN: 4828

European-Finnish (FIN) AF: 0.0586 AC: 622 AN: 10610

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0452 AC: 3071 AN: 68016

Other (OTH) AF: 0.0754 AC: 159 AN: 2110

Alfa AF: 0.0614 Hom.: 2100

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
LIST_S2	Benign	0.32	.;T;T
MetaRNN	Benign	0.0049	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L;L;.
PhyloP100		1.7
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
PromoterAI		0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.30
Mutation Taster		=96/4	polymorphism (auto)

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