1-209938201-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000637265.1(SYT14):c.-610C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000469 in 1,478,348 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (2 hom.)
• Consequence: SYT14 ENST00000637265.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.261

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-209938201-C-T is Benign according to our data. Variant chr1-209938201-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1804620.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT14	NM_001146262.4			upstream_gene_variant		ENST00000367019.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT14	ENST00000367019.6			upstream_gene_variant		1	NM_001146262.4

Frequencies

GnomAD3 genomes AF: 0.00277 AC: 420 AN: 151552 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00977

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000855

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000962

GnomAD3 exomes AF: 0.000365 AC: 49 AN: 134206 Hom.: 0 AF XY: 0.000204 AC XY: 15 AN XY: 73660

Gnomad AFR exome AF: 0.00897

Gnomad AMR exome AF: 0.000192

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000203 AC: 269 AN: 1326688 Hom.: 2 Cov.: 30 AF XY: 0.000180 AC XY: 118 AN XY: 656568

Gnomad4 AFR exome AF: 0.00824

Gnomad4 AMR exome AF: 0.000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000534

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000289

Gnomad4 OTH exome AF: 0.000582

GnomAD4 genome AF: 0.00280 AC: 425 AN: 151660 Hom.: 6 Cov.: 32 AF XY: 0.00286 AC XY: 212 AN XY: 74144

Gnomad4 AFR AF: 0.00986

Gnomad4 AMR AF: 0.000854

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000951

Alfa AF: 0.00143 Hom.: 0

Bravo AF: 0.00309

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 21, 2022

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	11
Dann	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs542912482; hg19: chr1-210111546;