rs10489346

Variant names:

• chr1-210061963-A-G
• rs10489346
• NM_001146262.4:c.443-32359A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146262.4(SYT14):​c.443-32359A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 151,740 control chromosomes in the GnomAD database, including 1,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.050 (1038 hom., cov: 32)
• Consequence: SYT14 NM_001146262.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• 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: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 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.443-32359A>G		intron	N/A	NP_001139734.1	Q8NB59-6
	SYT14	NM_001397544.1		c.1313-32359A>G		intron	N/A	NP_001384473.1	A0A8V8TN09
	SYT14	NM_001397545.1		c.1313-32359A>G		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.443-32359A>G		intron	N/A	ENSP00000355986.1	Q8NB59-6
	SYT14	ENST00000472886.5	TSL:1	c.443-32359A>G		intron	N/A	ENSP00000418901.1	Q8NB59-1
	SYT14	ENST00000367015.5	TSL:1	c.329-32359A>G		intron	N/A	ENSP00000355982.1	Q8NB59-3

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7583 AN: 151622 Hom.: 1035 Cov.: 32

Gnomad AFR AF: 0.00906

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.0985

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00956

Gnomad OTH AF: 0.0537

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

GnomAD4 genome AF: 0.0500 AC: 7592 AN: 151740 Hom.: 1038 Cov.: 32 AF XY: 0.0574 AC XY: 4259 AN XY: 74148

African (AFR) AF: 0.00904 AC: 375 AN: 41490

American (AMR) AF: 0.234 AC: 3561 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3460

East Asian (EAS) AF: 0.419 AC: 2160 AN: 5156

South Asian (SAS) AF: 0.0982 AC: 473 AN: 4816

European-Finnish (FIN) AF: 0.0179 AC: 189 AN: 10564

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00956 AC: 648 AN: 67750

Other (OTH) AF: 0.0536 AC: 113 AN: 2108

Alfa AF: 0.0259 Hom.: 41

Bravo AF: 0.0693

Asia WGS AF: 0.216 AC: 753 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.8
DANN	Benign	0.68
PhyloP100		-0.49
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10489346;

hg19: chr1-210235308;