chr20-1308941-A-G

Position:

• chr20-1308941-A-G

Variant summary

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

The NM_001318234.2(SNPH):​c.*2887A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 152,398 control chromosomes in the GnomAD database, including 159 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 0.038 (159 hom., cov: 33)
  • Exomes 𝑓: 0.015 (0 hom.)
• Consequence: SNPH NM_001318234.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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=-0.48).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNPH	NM_001318234.2	c.*2887A>G		3_prime_UTR_variant	7/7	ENST00000381867.6	NP_001305163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNPH	ENST00000381867.6	c.*2887A>G		3_prime_UTR_variant	7/7	1	NM_001318234.2	ENSP00000371291.1
SNPH	ENST00000614659.1	c.*2887A>G		3_prime_UTR_variant	4/4	1		ENSP00000479696.1
SNPH	ENST00000381873.7	c.*2887A>G		3_prime_UTR_variant	6/6	1		ENSP00000371297.3

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5831 AN: 152212 Hom.: 159 Cov.: 33

Gnomad AFR AF: 0.00900

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0555

Gnomad OTH AF: 0.0483

GnomAD4 exome AF: 0.0147 AC: 1 AN: 68 Hom.: 0 Cov.: 0 AF XY: 0.0192 AC XY: 1 AN XY: 52

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0179

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0383 AC: 5831 AN: 152330 Hom.: 159 Cov.: 33 AF XY: 0.0380 AC XY: 2832 AN XY: 74482

Gnomad4 AFR AF: 0.00897

Gnomad4 AMR AF: 0.0330

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0650

Gnomad4 FIN AF: 0.0277

Gnomad4 NFE AF: 0.0555

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0556 Hom.: 144

Bravo AF: 0.0374

Asia WGS AF: 0.0320 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.77

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: rs13163; hg19: chr20-1289585;