NM_138780.3:c.1350T>A

Variant names:

• chrX-38108615-T-A
• rs5918476
• NM_138780.3:c.1350T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138780.3(SYTL5):​c.1350T>A​(p.Tyr450*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: SYTL5 NM_138780.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 5 publications found

Genes affected

SYTL5 (HGNC:15589): (synaptotagmin like 5) The protein encoded by this gene belongs to the synaptotagmin-like (Slp) protein family, which contains a unique homology domain at the N-terminus, referred to as the Slp homology domain (SHD). The SHD functions as a binding site for Rab27A, which plays a role in protein transport. Expression of this gene is restricted to placenta and liver, suggesting that it might be involved in Rab27A-dependent membrane trafficking in specific tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138780.3. 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
	SYTL5	NM_138780.3	MANE Select	c.1350T>A	p.Tyr450*	stop_gained	Exon 12 of 17	NP_620135.1
	SYTL5	NM_001163334.1		c.1416T>A	p.Tyr472*	stop_gained	Exon 12 of 17	NP_001156806.1
	SYTL5	NM_001163335.2		c.1350T>A	p.Tyr450*	stop_gained	Exon 13 of 18	NP_001156807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYTL5	ENST00000297875.7	TSL:5 MANE Select	c.1350T>A	p.Tyr450*	stop_gained	Exon 12 of 17	ENSP00000297875.2
	SYTL5	ENST00000456733.2	TSL:1	c.1416T>A	p.Tyr472*	stop_gained	Exon 12 of 17	ENSP00000395220.2
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-557506T>A		intron	N/A	ENSP00000417050.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	36
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.81	D
PhyloP100		0.29
Vest4		0.38
GERP RS		2.2
Mutation Taster		=7/193	disease causing (fs/PTC)

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: rs5918476; hg19: chrX-37967868;