1-209937897-A-T

Variant names:

• chr1-209937897-A-T
• rs6692116
• ENST00000652023.1:n.52-14812A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000652023.1(SYT14):​n.52-14812A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 151,588 control chromosomes in the GnomAD database, including 3,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (3182 hom., cov: 30)
• Consequence: SYT14 ENST00000652023.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.182
• Publications: 0 publications found

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]

SYT14 Gene-Disease associations (from GenCC):

• autosomal recessive spinocerebellar ataxia 11

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-209937897-A-T is Benign according to our data. Variant chr1-209937897-A-T is described in ClinVar as Benign. ClinVar VariationId is 1261366.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652023.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT14	ENST00000652023.1		n.52-14812A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17557 AN: 151476 Hom.: 3173 Cov.: 30

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.0116

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00228

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.00762

Gnomad OTH AF: 0.0904

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

GnomAD4 genome AF: 0.116 AC: 17597 AN: 151588 Hom.: 3182 Cov.: 30 AF XY: 0.112 AC XY: 8325 AN XY: 74090

African (AFR) AF: 0.388 AC: 16034 AN: 41272

American (AMR) AF: 0.0480 AC: 732 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 40 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5106

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4818

European-Finnish (FIN) AF: 0.00228 AC: 24 AN: 10516

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.00761 AC: 516 AN: 67838

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.0717 Hom.: 238

Bravo AF: 0.131

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.50
PhyloP100		-0.18
PromoterAI		0.0015	Neutral

Splicing

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

Other links and lift over

dbSNP: rs6692116; hg19: chr1-210111242;