X-38073633-A-T

Variant names:

• chrX-38073633-A-T
• rs4827330
• NM_138780.3:c.489A>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_138780.3(SYTL5):​c.489A>T​(p.Ala163Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SYTL5 NM_138780.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 9 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-0.198 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL5	NM_138780.3	c.489A>T	p.Ala163Ala	synonymous_variant	Exon 5 of 17	ENST00000297875.7	NP_620135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYTL5	ENST00000297875.7	c.489A>T	p.Ala163Ala	synonymous_variant	Exon 5 of 17	5	NM_138780.3	ENSP00000297875.2
SYTL5	ENST00000456733.2	c.489A>T	p.Ala163Ala	synonymous_variant	Exon 4 of 17	1		ENSP00000395220.2
ENSG00000250349	ENST00000465127.1	c.172-592488A>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1085507 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 354273

African (AFR) AF: 0.00 AC: 0 AN: 26187

American (AMR) AF: 0.00 AC: 0 AN: 33296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19110

East Asian (EAS) AF: 0.00 AC: 0 AN: 29910

South Asian (SAS) AF: 0.00 AC: 0 AN: 51652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39813

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4068

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 835779

Other (OTH) AF: 0.00 AC: 0 AN: 45692

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.93
DANN	Benign	0.64
PhyloP100		-0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4827330; hg19: chrX-37932886;