1-209938388-G-A

Position:

• chr1-209938388-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001146262.4(SYT14):​c.13+111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,153,960 control chromosomes in the GnomAD database, including 168,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (16038 hom., cov: 32)
  • Exomes 𝑓: 0.55 (152167 hom.)
• Consequence: SYT14 NM_001146262.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.39

Genes affected

SYT14 (HGNC:23143): (synaptotagmin 14) This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate membrane trafficking in synaptic transmission. The encoded protein is a calcium-independent synaptotagmin. Mutations in this gene are a cause of autosomal recessive spinocerebellar ataxia-11 (SCAR11), and a t(1;3) translocation of this gene has been associated with neurodevelopmental abnormalities. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-209938388-G-A is Benign according to our data. Variant chr1-209938388-G-A is described in ClinVar as [Benign]. Clinvar id is 1238189.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT14	NM_001146262.4	c.13+111G>A		intron_variant		ENST00000367019.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT14	ENST00000367019.6	c.13+111G>A		intron_variant		1	NM_001146262.4

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64606 AN: 151304 Hom.: 16032 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.546 AC: 547133 AN: 1002548 Hom.: 152167 AF XY: 0.548 AC XY: 276916 AN XY: 505780

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.553

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.492

Gnomad4 NFE exome AF: 0.570

Gnomad4 OTH exome AF: 0.526

GnomAD4 genome AF: 0.427 AC: 64619 AN: 151412 Hom.: 16038 Cov.: 32 AF XY: 0.425 AC XY: 31438 AN XY: 74016

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.467

Alfa AF: 0.463 Hom.: 2613

Bravo AF: 0.413

Asia WGS AF: 0.473 AC: 1597 AN: 3388

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
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: rs12025114; hg19: chr1-210111733; COSMIC: COSV65411286;