rs149170280

Variant names:

• chr1-210013773-A-G
• rs149170280
• NM_001146262.4:c.202A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001146262.4(SYT14):​c.202A>G​(p.Arg68Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000778 in 1,612,266 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00082 (1 hom.)
• Consequence: SYT14 NM_001146262.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 5.23
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06872484).

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.202A>G	p.Arg68Gly	missense	Exon 3 of 9	NP_001139734.1	Q8NB59-6
	SYT14	NM_001146261.4		c.337A>G	p.Arg113Gly	missense	Exon 4 of 10	NP_001139733.1	Q8NB59-7
	SYT14	NM_001146264.4		c.337A>G	p.Arg113Gly	missense	Exon 4 of 9	NP_001139736.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT14	ENST00000367019.6	TSL:1 MANE Select	c.202A>G	p.Arg68Gly	missense	Exon 3 of 9	ENSP00000355986.1	Q8NB59-6
	SYT14	ENST00000472886.5	TSL:1	c.202A>G	p.Arg68Gly	missense	Exon 3 of 8	ENSP00000418901.1	Q8NB59-1
	SYT14	ENST00000367015.5	TSL:1	c.88A>G	p.Arg30Gly	missense	Exon 3 of 8	ENSP00000355982.1	Q8NB59-3

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 63 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000324 AC: 81 AN: 250216 AF XY: 0.000288

Gnomad AFR exome AF: 0.0000627

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000626

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000816 AC: 1192 AN: 1460106 Hom.: 1 Cov.: 31 AF XY: 0.000756 AC XY: 549 AN XY: 726244

African (AFR) AF: 0.000210 AC: 7 AN: 33400

American (AMR) AF: 0.000112 AC: 5 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.00 AC: 0 AN: 85832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5330

European-Non Finnish (NFE) AF: 0.000997 AC: 1108 AN: 1111588

Other (OTH) AF: 0.00118 AC: 71 AN: 60274

GnomAD4 genome AF: 0.000414 AC: 63 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74330

African (AFR) AF: 0.0000724 AC: 3 AN: 41448

American (AMR) AF: 0.000131 AC: 2 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000838 AC: 57 AN: 68004

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000645 Hom.: 0

Bravo AF: 0.000400

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000288 AC: 35

EpiCase AF: 0.00109

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.018
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N
PhyloP100		5.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.089
Sift	Uncertain	0.018	D
Sift4G	Benign	0.35	T
Polyphen		0.10	B
Vest4		0.36
MVP		0.043
ClinPred		0.042	T
GERP RS		3.9
Varity_R		0.087
gMVP		0.33
Mutation Taster		=78/22	polymorphism

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: rs149170280; hg19: chr1-210187118;