1-209938148-C-T

Variant names:

• chr1-209938148-C-T
• rs139994721
• ENST00000652023.1:n.52-14561C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000652023.1(SYT14):​n.52-14561C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 1,154,452 control chromosomes in the GnomAD database, including 2,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (605 hom., cov: 32)
  • Exomes 𝑓: 0.015 (2176 hom.)
• Consequence: SYT14 ENST00000652023.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-209938148-C-T is Benign according to our data. Variant chr1-209938148-C-T is described in ClinVar as Benign. ClinVar VariationId is 1181007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.228 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
	SYT14	NM_001146262.4	MANE Select	c.-117C>T		upstream_gene	N/A	NP_001139734.1	Q8NB59-6
	SYT14	NM_001397544.1		c.-1166C>T		upstream_gene	N/A	NP_001384473.1	A0A8V8TN09
	SYT14	NM_001397545.1		c.-1371C>T		upstream_gene	N/A	NP_001384474.1	A0A8V8TN09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT14	ENST00000652023.1		n.52-14561C>T		intron	N/A
	SYT14	ENST00000367019.6	TSL:1 MANE Select	c.-117C>T		upstream_gene	N/A	ENSP00000355986.1	Q8NB59-6
	SYT14	ENST00000472886.5	TSL:1	c.-117C>T		upstream_gene	N/A	ENSP00000418901.1	Q8NB59-1

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5198 AN: 149800 Hom.: 597 Cov.: 32

Gnomad AFR AF: 0.00662

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.0162

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.00997

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00269

Gnomad OTH AF: 0.0411

GnomAD2 exomes AF: 0.0905 AC: 6435 AN: 71120 AF XY: 0.0657

Gnomad AFR exome AF: 0.00526

Gnomad AMR exome AF: 0.428

Gnomad ASJ exome AF: 0.0178

Gnomad EAS exome AF: 0.179

Gnomad FIN exome AF: 0.0105

Gnomad NFE exome AF: 0.00232

Gnomad OTH exome AF: 0.0546

GnomAD4 exome AF: 0.0154 AC: 15489 AN: 1004552 Hom.: 2176 Cov.: 13 AF XY: 0.0142 AC XY: 7070 AN XY: 498092

African (AFR) AF: 0.00304 AC: 60 AN: 19718

American (AMR) AF: 0.387 AC: 8084 AN: 20906

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 323 AN: 16226

East Asian (EAS) AF: 0.178 AC: 3683 AN: 20678

South Asian (SAS) AF: 0.0186 AC: 918 AN: 49414

European-Finnish (FIN) AF: 0.0108 AC: 369 AN: 34064

Middle Eastern (MID) AF: 0.00717 AC: 21 AN: 2928

European-Non Finnish (NFE) AF: 0.00125 AC: 1002 AN: 801516

Other (OTH) AF: 0.0263 AC: 1029 AN: 39102

GnomAD4 genome AF: 0.0348 AC: 5217 AN: 149900 Hom.: 605 Cov.: 32 AF XY: 0.0405 AC XY: 2972 AN XY: 73326

African (AFR) AF: 0.00660 AC: 264 AN: 39990

American (AMR) AF: 0.235 AC: 3561 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.0162 AC: 56 AN: 3456

East Asian (EAS) AF: 0.166 AC: 849 AN: 5110

South Asian (SAS) AF: 0.0236 AC: 114 AN: 4824

European-Finnish (FIN) AF: 0.00997 AC: 103 AN: 10326

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00269 AC: 182 AN: 67734

Other (OTH) AF: 0.0412 AC: 86 AN: 2088

Alfa AF: 0.0171 Hom.: 30

Bravo AF: 0.0548

Asia WGS AF: 0.0890 AC: 303 AN: 3426

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Uncertain	0.98
PhyloP100		1.2
PromoterAI		0.0081	Neutral

Splicing

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

Other links and lift over

dbSNP: rs139994721; hg19: chr1-210111493;