rs3803947

chr20-1308322-G-A

Variant summary

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

The NM_001318234.2(SNPH):c.*2268G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,442 control chromosomes in the GnomAD database, including 17,360 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (17337 hom., cov: 33)
  • Exomes 𝑓: 0.37 (23 hom.)
• Consequence: SNPH NM_001318234.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

Genes affected

SNPH (HGNC:15931): (syntaphilin) Syntaxin-1, synaptobrevin/VAMP, and SNAP25 interact to form the SNARE complex, which is required for synaptic vesicle docking and fusion. The protein encoded by this gene is membrane-associated and inhibits SNARE complex formation by binding free syntaxin-1. Expression of this gene appears to be brain-specific. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNPH	NM_001318234.2	c.*2268G>A		3_prime_UTR_variant	7/7	ENST00000381867.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNPH	ENST00000381867.6	c.*2268G>A		3_prime_UTR_variant	7/7	1	NM_001318234.2	P3
SNPH	ENST00000381873.7	c.*2268G>A		3_prime_UTR_variant	6/6	1		A1
SNPH	ENST00000614659.1	c.*2268G>A		3_prime_UTR_variant	4/4	1		P3

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70865 AN: 152012 Hom.: 17316 Cov.: 33

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.0901

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.372 AC: 116 AN: 312 Hom.: 23 Cov.: 0 AF XY: 0.376 AC XY: 88 AN XY: 234

Gnomad4 AFR exome AF: 0.667

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.384

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.466 AC: 70924 AN: 152130 Hom.: 17337 Cov.: 33 AF XY: 0.455 AC XY: 33841 AN XY: 74360

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.0895

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.455

Alfa AF: 0.463 Hom.: 2085

Bravo AF: 0.474

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.4
Dann	Benign	0.87

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: rs3803947; hg19: chr20-1288966;