1-210100178-GT-AC

Variant names:

• chr1-210100178-GT-AC
• NM_001146262.4:c.881_882delGTinsAC
• SYT14 p.Gly294Asp

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001146262.4(SYT14):​c.881_882delGTinsAC​(p.Gly294Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYT14 NM_001146262.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23
• 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: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.881_882delGTinsAC	p.Gly294Asp	missense	N/A	NP_001139734.1	Q8NB59-6
	SYT14	NM_001397544.1		c.1751_1752delGTinsAC	p.Gly584Asp	missense	N/A	NP_001384473.1	A0A8V8TN09
	SYT14	NM_001397545.1		c.1751_1752delGTinsAC	p.Gly584Asp	missense	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.881_882delGTinsAC	p.Gly294Asp	missense	N/A	ENSP00000355986.1	Q8NB59-6
	SYT14	ENST00000472886.5	TSL:1	c.881_882delGTinsAC	p.Gly294Asp	missense	N/A	ENSP00000418901.1	Q8NB59-1
	SYT14	ENST00000367015.5	TSL:1	c.767_768delGTinsAC	p.Gly256Asp	missense	N/A	ENSP00000355982.1	Q8NB59-3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.2

Splicing

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

hg19: chr1-210273523;