rs71515148

Positions:

• chr1-210021220-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001146262.4(SYT14):​c.408T>C​(p.Tyr136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,614,030 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (11 hom.)
• Consequence: SYT14 NM_001146262.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.30

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 1-210021220-T-C is Benign according to our data. Variant chr1-210021220-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 586696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-210021220-T-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT14	NM_001146262.4	c.408T>C	p.Tyr136=	synonymous_variant	4/9	ENST00000367019.6	NP_001139734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT14	ENST00000367019.6	c.408T>C	p.Tyr136=	synonymous_variant	4/9	1	NM_001146262.4	ENSP00000355986

Frequencies

GnomAD3 genomes AF: 0.00179 AC: 273 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00298

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00191 AC: 480 AN: 251026 Hom.: 1 AF XY: 0.00203 AC XY: 276 AN XY: 135654

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00386

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00273

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00293 AC: 4290 AN: 1461702 Hom.: 11 Cov.: 31 AF XY: 0.00303 AC XY: 2203 AN XY: 727164

Gnomad4 AFR exome AF: 0.000448

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00408

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.00332

Gnomad4 OTH exome AF: 0.00263

GnomAD4 genome AF: 0.00180 AC: 274 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.00165 AC XY: 123 AN XY: 74496

Gnomad4 AFR AF: 0.000673

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00298

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00259 Hom.: 1

Bravo AF: 0.00172

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00365

EpiControl AF: 0.00290

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	SYT14: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.2
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs71515148; hg19: chr1-210194565;