chr12-78921400-G-A

Position:

• chr12-78921400-G-A

Variant summary

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

The NM_005639.3(SYT1):​c.-217+56291G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 151,934 control chromosomes in the GnomAD database, including 840 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 0.089 (840 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

Genes affected

SYT1 (HGNC:11509): (synaptotagmin 1) This gene encodes a member of the synaptotagmin protein family. The synaptotagmins are integral membrane proteins of synaptic vesicles that serve as calcium sensors in the process of vesicular trafficking and exocytosis. The encoded protein participates in triggering neurotransmitter release at the synapse in response to calcium binding. Mutations in this gene are associated with Baker-Gordon syndrome. [provided by RefSeq, Jan 2023]

LOC105369863 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT1	NM_005639.3	c.-217+56291G>A		intron_variant		ENST00000261205.9
LOC105369863	XR_007063385.1	n.30713-16244C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT1	ENST00000261205.9	c.-217+56291G>A		intron_variant		1	NM_005639.3	P3

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13468 AN: 151816 Hom.: 829 Cov.: 32

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0932

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0889 AC: 13501 AN: 151934 Hom.: 840 Cov.: 32 AF XY: 0.0962 AC XY: 7144 AN XY: 74264

Gnomad4 AFR AF: 0.0645

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.0744

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.0657

Gnomad4 OTH AF: 0.0984

Alfa AF: 0.0717 Hom.: 608

Bravo AF: 0.0895

Asia WGS AF: 0.176 AC: 608 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.62

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: rs1569033; hg19: chr12-79315180;