1-209966161-C-T

Variant names:

• chr1-209966161-C-T
• rs9803620
• NM_001146262.4:c.61+13405C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146262.4. 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
	SYT14	NM_001146262.4	MANE Select	c.61+13405C>T		intron	N/A	NP_001139734.1	Q8NB59-6
	SYT14	NM_001397544.1		c.-989+13405C>T		intron	N/A	NP_001384473.1	A0A8V8TN09
	SYT14	NM_001397545.1		c.-989+12902C>T		intron	N/A	NP_001384474.1	A0A8V8TN09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT14	ENST00000367019.6	TSL:1 MANE Select	c.61+13405C>T		intron	N/A	ENSP00000355986.1	Q8NB59-6
	SYT14	ENST00000472886.5	TSL:1	c.61+13405C>T		intron	N/A	ENSP00000418901.1	Q8NB59-1
	SYT14	ENST00000367015.5	TSL:1	c.-54+12902C>T		intron	N/A	ENSP00000355982.1	Q8NB59-3

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

African (AFR) AF: 0.470 AC: 1476 AN: 3138

American (AMR) AF: 0.0318 AC: 201 AN: 6322

Ashkenazi Jewish (ASJ) AF: 0.0189 AC: 52 AN: 2754

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00364 AC: 89 AN: 24466

European-Finnish (FIN) AF: 0.00371 AC: 23 AN: 6206

Middle Eastern (MID) AF: 0.0619 AC: 27 AN: 436

European-Non Finnish (NFE) AF: 0.00698 AC: 499 AN: 71442

Other (OTH) AF: 0.0312 AC: 196 AN: 6288

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

African (AFR) AF: 0.462 AC: 19122 AN: 41432

American (AMR) AF: 0.0553 AC: 844 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4820

European-Finnish (FIN) AF: 0.00236 AC: 25 AN: 10596

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.00788 AC: 536 AN: 67998

Other (OTH) AF: 0.104 AC: 220 AN: 2110

Alfa AF: 0.0849 Hom.: 335

Bravo AF: 0.155

Asia WGS AF: 0.0310 AC: 109 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	-1.0
CADD	Benign	0.91
DANN	Benign	0.65
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9803620; hg19: chr1-210139506;