rs2307890

Variant names:

• chr1-210094548-TGAA-T
• rs2307890
• NM_001146262.4:c.675_677delAGA

Your query was ambiguous. Multiple possible variants found:

• chr1-210094548-TGAA-T
• chr1-210094548-TGAA-TGAAGAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PM4_Supporting BP6 BA1

The NM_001146262.4(SYT14):​c.675_677delAGA​(p.Glu225del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,578 control chromosomes in the GnomAD database, including 14,767 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.10 (1090 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13677 hom.)
• Consequence: SYT14 NM_001146262.4 disruptive_inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:4
• Conservation: PhyloP100: 9.35
• Publications: 6 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 -8 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001146262.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 1-210094548-TGAA-T is Benign according to our data. Variant chr1-210094548-TGAA-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 212360.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 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.675_677delAGA	p.Glu225del	disruptive_inframe_deletion	Exon 5 of 9	NP_001139734.1	Q8NB59-6
	SYT14	NM_001397544.1		c.1545_1547delAGA	p.Glu515del	disruptive_inframe_deletion	Exon 6 of 9	NP_001384473.1	A0A8V8TN09
	SYT14	NM_001397545.1		c.1545_1547delAGA	p.Glu515del	disruptive_inframe_deletion	Exon 7 of 10	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.675_677delAGA	p.Glu225del	disruptive_inframe_deletion	Exon 5 of 9	ENSP00000355986.1	Q8NB59-6
	SYT14	ENST00000472886.5	TSL:1	c.675_677delAGA	p.Glu225del	disruptive_inframe_deletion	Exon 5 of 8	ENSP00000418901.1	Q8NB59-1
	SYT14	ENST00000367015.5	TSL:1	c.561_563delAGA	p.Glu187del	disruptive_inframe_deletion	Exon 5 of 8	ENSP00000355982.1	Q8NB59-3

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15575 AN: 152042 Hom.: 1091 Cov.: 31

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0714

Gnomad EAS AF: 0.0866

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.0909

GnomAD2 exomes AF: 0.116 AC: 29060 AN: 249712 AF XY: 0.120

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.0564

Gnomad ASJ exome AF: 0.0691

Gnomad EAS exome AF: 0.0755

Gnomad FIN exome AF: 0.217

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.132 AC: 193418 AN: 1461418 Hom.: 13677 AF XY: 0.133 AC XY: 96390 AN XY: 726994

African (AFR) AF: 0.0202 AC: 675 AN: 33468

American (AMR) AF: 0.0601 AC: 2682 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.0707 AC: 1848 AN: 26132

East Asian (EAS) AF: 0.102 AC: 4055 AN: 39686

South Asian (SAS) AF: 0.121 AC: 10457 AN: 86244

European-Finnish (FIN) AF: 0.214 AC: 11404 AN: 53348

Middle Eastern (MID) AF: 0.0961 AC: 554 AN: 5766

European-Non Finnish (NFE) AF: 0.139 AC: 154593 AN: 1111744

Other (OTH) AF: 0.118 AC: 7150 AN: 60376

GnomAD4 genome AF: 0.102 AC: 15572 AN: 152160 Hom.: 1090 Cov.: 31 AF XY: 0.107 AC XY: 7943 AN XY: 74370

African (AFR) AF: 0.0247 AC: 1028 AN: 41536

American (AMR) AF: 0.0763 AC: 1167 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 248 AN: 3472

East Asian (EAS) AF: 0.0866 AC: 449 AN: 5182

South Asian (SAS) AF: 0.129 AC: 624 AN: 4820

European-Finnish (FIN) AF: 0.225 AC: 2379 AN: 10570

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9306 AN: 67976

Other (OTH) AF: 0.0900 AC: 190 AN: 2112

Alfa AF: 0.113 Hom.: 224

Bravo AF: 0.0875

Asia WGS AF: 0.0840 AC: 294 AN: 3478

EpiCase AF: 0.132

EpiControl AF: 0.135

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	3	Autosomal recessive spinocerebellar ataxia 11 (3)
-	-	1	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.4
Mutation Taster		=45/55	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2307890; hg19: chr1-210267893; COSMIC: COSV55049400;