1-209938148-C-T

Variant summary

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

The ENST00000652023.1(SYT14):n.52-14561C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 1,154,452 control chromosomes in the GnomAD database, including 2,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (605 hom., cov: 32)
  • Exomes 𝑓: 0.015 (2176 hom.)
• Consequence: SYT14 ENST00000652023.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.24

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=-0.53).
• BP6: Variant 1-209938148-C-T is Benign according to our data. Variant chr1-209938148-C-T is described in ClinVar as [Benign]. Clinvar id is 1181007.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT14	ENST00000652023.1	n.52-14561C>T		intron_variant, non_coding_transcript_variant
SYT14	ENST00000537238.5			upstream_gene_variant		5
SYT14	ENST00000637265.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5198 AN: 149800 Hom.: 597 Cov.: 32

Gnomad AFR AF: 0.00662

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.0162

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.00997

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00269

Gnomad OTH AF: 0.0411

GnomAD3 exomes AF: 0.0905 AC: 6435 AN: 71120 Hom.: 1343 AF XY: 0.0657 AC XY: 2659 AN XY: 40476

Gnomad AFR exome AF: 0.00526

Gnomad AMR exome AF: 0.428

Gnomad ASJ exome AF: 0.0178

Gnomad EAS exome AF: 0.179

Gnomad SAS exome AF: 0.0171

Gnomad FIN exome AF: 0.0105

Gnomad NFE exome AF: 0.00232

Gnomad OTH exome AF: 0.0546

GnomAD4 exome AF: 0.0154 AC: 15489 AN: 1004552 Hom.: 2176 Cov.: 13 AF XY: 0.0142 AC XY: 7070 AN XY: 498092

Gnomad4 AFR exome AF: 0.00304

Gnomad4 AMR exome AF: 0.387

Gnomad4 ASJ exome AF: 0.0199

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.0186

Gnomad4 FIN exome AF: 0.0108

Gnomad4 NFE exome AF: 0.00125

Gnomad4 OTH exome AF: 0.0263

GnomAD4 genome AF: 0.0348 AC: 5217 AN: 149900 Hom.: 605 Cov.: 32 AF XY: 0.0405 AC XY: 2972 AN XY: 73326

Gnomad4 AFR AF: 0.00660

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.0162

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.0236

Gnomad4 FIN AF: 0.00997

Gnomad4 NFE AF: 0.00269

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0171 Hom.: 30

Bravo AF: 0.0548

Asia WGS AF: 0.0890 AC: 303 AN: 3426

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

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	17
Dann	Uncertain	0.98

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139994721; hg19: chr1-210111493;