1-209938260-G-A

Variant names:

• chr1-209938260-G-A
• rs749192802
• NM_001146262.4:c.-5G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001146261.4(SYT14):​c.10G>A​(p.Ala4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000853 in 1,407,560 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A4A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000085 (1 hom.)
• Consequence: SYT14 NM_001146261.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.412
• 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: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034314364).
• BP6: Variant 1-209938260-G-A is Benign according to our data. Variant chr1-209938260-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2270008.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146261.4. 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.-5G>A		5_prime_UTR	Exon 1 of 9	NP_001139734.1	Q8NB59-6
	SYT14	NM_001146261.4		c.10G>A	p.Ala4Thr	missense	Exon 1 of 10	NP_001139733.1	Q8NB59-7
	SYT14	NM_001146264.4		c.10G>A	p.Ala4Thr	missense	Exon 1 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.-5G>A		5_prime_UTR	Exon 1 of 9	ENSP00000355986.1	Q8NB59-6
	SYT14	ENST00000472886.5	TSL:1	c.-5G>A		5_prime_UTR	Exon 1 of 8	ENSP00000418901.1	Q8NB59-1
	SYT14	ENST00000399639.6	TSL:1	n.-324G>A		non_coding_transcript_exon	Exon 1 of 9	ENSP00000445837.2	Q8NB59-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000377 AC: 8 AN: 211992 AF XY: 0.0000344

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000717

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000104

Gnomad OTH exome AF: 0.000402

GnomAD4 exome AF: 0.00000853 AC: 12 AN: 1407560 Hom.: 1 Cov.: 30 AF XY: 0.00000714 AC XY: 5 AN XY: 700086

African (AFR) AF: 0.00 AC: 0 AN: 29488

American (AMR) AF: 0.000247 AC: 10 AN: 40454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24222

East Asian (EAS) AF: 0.0000289 AC: 1 AN: 34594

South Asian (SAS) AF: 0.00 AC: 0 AN: 81790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5546

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1082066

Other (OTH) AF: 0.00 AC: 0 AN: 57368

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000415 AC: 5

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.96
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0035	N
LIST_S2	Benign	0.24	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.89	T
PhyloP100		-0.41
PrimateAI	Uncertain	0.56	T
Vest4		0.14
MVP		0.043
ClinPred		0.049	T
GERP RS		-4.6
PromoterAI		-0.027	Neutral
gMVP		0.089
Mutation Taster		=96/4	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: rs749192802; hg19: chr1-210111605; COSMIC: COSV107457405;