rs2130627

Variant names:

• chr1-210117964-A-G
• rs2130627
• NM_001146262.4:c.1164+17503A>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.1164+17503A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,176 control chromosomes in the GnomAD database, including 4,734 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 0.14 (4734 hom., cov: 33)
• Consequence: SYT14 NM_001146262.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• 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, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT14	NM_001146262.4	c.1164+17503A>G		intron_variant	Intron 6 of 8	ENST00000367019.6	NP_001139734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT14	ENST00000367019.6	c.1164+17503A>G		intron_variant	Intron 6 of 8	1	NM_001146262.4	ENSP00000355986.1
SYT14	ENST00000534859.2	c.930+17503A>G		intron_variant	Intron 3 of 5	1		ENSP00000442891.2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21192 AN: 152058 Hom.: 4723 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0563

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.00748

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.140 AC: 21233 AN: 152176 Hom.: 4734 Cov.: 33 AF XY: 0.135 AC XY: 10033 AN XY: 74428

African (AFR) AF: 0.471 AC: 19542 AN: 41448

American (AMR) AF: 0.0562 AC: 860 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.00235 AC: 25 AN: 10624

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.00747 AC: 508 AN: 68010

Other (OTH) AF: 0.104 AC: 219 AN: 2110

Alfa AF: 0.134 Hom.: 727

Bravo AF: 0.159

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.86
DANN	Benign	0.47
PhyloP100		-0.12
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: rs2130627; hg19: chr1-210291309;