1-209952535-T-C

Position:

• chr1-209952535-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000367019.6(SYT14):​c.14-174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 152,168 control chromosomes in the GnomAD database, including 1,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.087 (1797 hom., cov: 32)
• Consequence: SYT14 ENST00000367019.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.205

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-209952535-T-C is Benign according to our data. Variant chr1-209952535-T-C is described in ClinVar as [Benign]. Clinvar id is 1241939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT14	NM_001146262.4	c.14-174T>C		intron_variant		ENST00000367019.6	NP_001139734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT14	ENST00000367019.6	c.14-174T>C		intron_variant		1	NM_001146262.4	ENSP00000355986

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13191 AN: 152050 Hom.: 1795 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00681

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0868 AC: 13207 AN: 152168 Hom.: 1797 Cov.: 32 AF XY: 0.0840 AC XY: 6253 AN XY: 74426

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.0342

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.00679

Gnomad4 OTH AF: 0.0668

Alfa AF: 0.0557 Hom.: 135

Bravo AF: 0.0973

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 17, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.63

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: rs7530907; hg19: chr1-210125880;