1-209966161-C-T

Position:

• chr1-209966161-C-T

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.61+13405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 278,302 control chromosomes in the GnomAD database, including 4,855 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (4464 hom., cov: 31)
  • Exomes 𝑓: 0.020 (391 hom.)
• Consequence: SYT14 NM_001146262.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.935

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=-1.02).
• BP6: Variant 1-209966161-C-T is Benign according to our data. Variant chr1-209966161-C-T is described in ClinVar as [Benign]. Clinvar id is 1229055.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT14	NM_001146262.4	c.61+13405C>T		intron_variant		ENST00000367019.6	NP_001139734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT14	ENST00000367019.6	c.61+13405C>T		intron_variant		1	NM_001146262.4	ENSP00000355986

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20811 AN: 151950 Hom.: 4453 Cov.: 31

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.00790

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0203 AC: 2564 AN: 126234 Hom.: 391 AF XY: 0.0171 AC XY: 1175 AN XY: 68606

Gnomad4 AFR exome AF: 0.470

Gnomad4 AMR exome AF: 0.0318

Gnomad4 ASJ exome AF: 0.0189

Gnomad4 EAS exome AF: 0.000193

Gnomad4 SAS exome AF: 0.00364

Gnomad4 FIN exome AF: 0.00371

Gnomad4 NFE exome AF: 0.00698

Gnomad4 OTH exome AF: 0.0312

GnomAD4 genome AF: 0.137 AC: 20856 AN: 152068 Hom.: 4464 Cov.: 31 AF XY: 0.132 AC XY: 9811 AN XY: 74334

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.0553

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00236

Gnomad4 NFE AF: 0.00788

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0849 Hom.: 335

Bravo AF: 0.155

Asia WGS AF: 0.0310 AC: 109 AN: 3478

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

Jun 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.65

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: rs9803620; hg19: chr1-210139506;