rs542912482

Variant names:

• chr1-209938201-C-T
• rs542912482
• ENST00000637265.1:c.-610C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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), PanelApp Australia, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1804620.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000637265.1. 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
	SYT14	NM_001146262.4	MANE Select	c.-64C>T		upstream_gene	N/A	NP_001139734.1	Q8NB59-6
	SYT14	NM_001397544.1		c.-1113C>T		upstream_gene	N/A	NP_001384473.1	A0A8V8TN09
	SYT14	NM_001397545.1		c.-1318C>T		upstream_gene	N/A	NP_001384474.1	A0A8V8TN09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT14	ENST00000637265.1	TSL:5	c.-610C>T		5_prime_UTR	Exon 1 of 10	ENSP00000489897.1	A0A1B0GTZ1
	SYT14	ENST00000537238.5	TSL:5	c.-383C>T		5_prime_UTR	Exon 1 of 9	ENSP00000437423.1	Q8NB59-3
	SYT14	ENST00000652023.1		n.52-14508C>T		intron	N/A

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

GnomAD2 exomes AF: 0.000365 AC: 49 AN: 134206 AF XY: 0.000204

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 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

African (AFR) AF: 0.00824 AC: 223 AN: 27062

American (AMR) AF: 0.000226 AC: 7 AN: 30970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22188

East Asian (EAS) AF: 0.00 AC: 0 AN: 28502

South Asian (SAS) AF: 0.0000534 AC: 4 AN: 74888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47658

Middle Eastern (MID) AF: 0.000196 AC: 1 AN: 5098

European-Non Finnish (NFE) AF: 0.00000289 AC: 3 AN: 1037102

Other (OTH) AF: 0.000582 AC: 31 AN: 53220

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

African (AFR) AF: 0.00986 AC: 409 AN: 41468

American (AMR) AF: 0.000854 AC: 13 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67844

Other (OTH) AF: 0.000951 AC: 2 AN: 2102

Alfa AF: 0.00143 Hom.: 0

Bravo AF: 0.00309

ClinVar

ClinVar submissions

Significance: Likely 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	-0.76
CADD	Benign	11
DANN	Benign	0.92
PhyloP100		0.26
PromoterAI		0.47	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs542912482; hg19: chr1-210111546;