20-1308941-A-G

Variant names:

• chr20-1308941-A-G
• rs13163
• NM_001318234.2:c.*2887A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318234.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNPH	NM_001318234.2	MANE Select	c.*2887A>G		3_prime_UTR	Exon 7 of 7	NP_001305163.1
	SNPH	NM_001439257.1		c.*2887A>G		3_prime_UTR	Exon 7 of 7	NP_001426186.1
	SNPH	NM_001439258.1		c.*2887A>G		3_prime_UTR	Exon 6 of 6	NP_001426187.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNPH	ENST00000381867.6	TSL:1 MANE Select	c.*2887A>G		3_prime_UTR	Exon 7 of 7	ENSP00000371291.1
	SNPH	ENST00000614659.1	TSL:1	c.*2887A>G		3_prime_UTR	Exon 4 of 4	ENSP00000479696.1
	SNPH	ENST00000381873.7	TSL:1	c.*2887A>G		3_prime_UTR	Exon 6 of 6	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

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0179 AC: 1 AN: 56

Other (OTH) AF: 0.00 AC: 0 AN: 6

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

African (AFR) AF: 0.00897 AC: 373 AN: 41574

American (AMR) AF: 0.0330 AC: 505 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0650 AC: 314 AN: 4828

European-Finnish (FIN) AF: 0.0277 AC: 294 AN: 10622

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0555 AC: 3777 AN: 68018

Other (OTH) AF: 0.0482 AC: 102 AN: 2114

Alfa AF: 0.0560 Hom.: 154

Bravo AF: 0.0374

Asia WGS AF: 0.0320 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.77
PhyloP100		1.3
Mutation Taster		=100/0	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: rs13163; hg19: chr20-1289585;