1-209938238-G-C

Variant names:

• chr1-209938238-G-C
• rs1169227059
• NM_001146262.4:c.-27G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001146262.4(SYT14):​c.-27G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,720 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SYT14 NM_001146262.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• 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, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT14	NM_001146262.4	MANE Select	c.-27G>C		5_prime_UTR	Exon 1 of 9	NP_001139734.1
	SYT14	NR_027459.3		n.22G>C		non_coding_transcript_exon	Exon 1 of 9
	SYT14	NM_001397544.1		c.-1076G>C		5_prime_UTR	Exon 1 of 9	NP_001384473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT14	ENST00000367019.6	TSL:1 MANE Select	c.-27G>C		5_prime_UTR	Exon 1 of 9	ENSP00000355986.1
	SYT14	ENST00000637265.1	TSL:5	c.-573G>C		5_prime_UTR	Exon 1 of 10	ENSP00000489897.1
	SYT14	ENST00000699295.1		c.-1281G>C		5_prime_UTR	Exon 1 of 10	ENSP00000514275.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1391720 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 691472

African (AFR) AF: 0.00 AC: 0 AN: 28734

American (AMR) AF: 0.00 AC: 0 AN: 38626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23722

East Asian (EAS) AF: 0.00 AC: 0 AN: 33024

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5470

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074124

Other (OTH) AF: 0.00 AC: 0 AN: 56578

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.0
DANN	Benign	0.68
PhyloP100		-0.084
PromoterAI		-0.039	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1169227059; hg19: chr1-210111583;