chr1-209952535-T-C

Variant names:

• chr1-209952535-T-C
• rs7530907
• NM_001146262.4:c.14-174T>C

Variant summary

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

The NM_001146262.4(SYT14):​c.14-174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 152,168 control chromosomes in the GnomAD database, including 1,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.087 (1797 hom., cov: 32)
• Consequence: SYT14 NM_001146262.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.205
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-209952535-T-C is Benign according to our data. Variant chr1-209952535-T-C is described in ClinVar as Benign. ClinVar VariationId is 1241939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 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.14-174T>C		intron	N/A	NP_001139734.1	Q8NB59-6
	SYT14	NM_001397544.1		c.-1036-174T>C		intron	N/A	NP_001384473.1	A0A8V8TN09
	SYT14	NM_001397545.1		c.-1241-174T>C		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.14-174T>C		intron	N/A	ENSP00000355986.1	Q8NB59-6
	SYT14	ENST00000472886.5	TSL:1	c.14-174T>C		intron	N/A	ENSP00000418901.1	Q8NB59-1
	SYT14	ENST00000399639.6	TSL:1	n.-306-174T>C		intron	N/A	ENSP00000445837.2	Q8NB59-4

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13191 AN: 152050 Hom.: 1795 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00681

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0868 AC: 13207 AN: 152168 Hom.: 1797 Cov.: 32 AF XY: 0.0840 AC XY: 6253 AN XY: 74426

African (AFR) AF: 0.289 AC: 11989 AN: 41432

American (AMR) AF: 0.0342 AC: 523 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4828

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10622

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00679 AC: 462 AN: 68020

Other (OTH) AF: 0.0668 AC: 141 AN: 2112

Alfa AF: 0.0557 Hom.: 135

Bravo AF: 0.0973

Asia WGS AF: 0.0180 AC: 62 AN: 3478

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	-0.87
CADD	Benign	5.8
DANN	Benign	0.63
PhyloP100		-0.20
PromoterAI		-0.0054	Neutral
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: rs7530907; hg19: chr1-210125880;