NM_138780.3:c.329+7287C>T

Variant names:

• chrX-38061709-C-T
• rs2024917
• NM_138780.3:c.329+7287C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138780.3(SYTL5):​c.329+7287C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 110,586 control chromosomes in the GnomAD database, including 3,932 homozygotes. There are 9,253 hemizygotes in GnomAD. 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: 𝑓 0.29 (3932 hom., 9253 hem., cov: 23)
• Consequence: SYTL5 NM_138780.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL5	NM_138780.3	c.329+7287C>T		intron_variant	Intron 3 of 16	ENST00000297875.7	NP_620135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYTL5	ENST00000297875.7	c.329+7287C>T		intron_variant	Intron 3 of 16	5	NM_138780.3	ENSP00000297875.2
SYTL5	ENST00000456733.2	c.329+7287C>T		intron_variant	Intron 2 of 16	1		ENSP00000395220.2
ENSG00000250349	ENST00000465127.1	c.172-604412C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 32432 AN: 110536 Hom.: 3930 Cov.: 23

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0984

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.317

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 32439 AN: 110586 Hom.: 3932 Cov.: 23 AF XY: 0.281 AC XY: 9253 AN XY: 32880

African (AFR) AF: 0.420 AC: 12764 AN: 30366

American (AMR) AF: 0.344 AC: 3577 AN: 10389

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 621 AN: 2633

East Asian (EAS) AF: 0.0978 AC: 344 AN: 3516

South Asian (SAS) AF: 0.372 AC: 963 AN: 2588

European-Finnish (FIN) AF: 0.123 AC: 731 AN: 5941

Middle Eastern (MID) AF: 0.347 AC: 75 AN: 216

European-Non Finnish (NFE) AF: 0.242 AC: 12746 AN: 52755

Other (OTH) AF: 0.313 AC: 471 AN: 1506

Alfa AF: 0.272 Hom.: 14869

Bravo AF: 0.317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.6
DANN	Benign	0.52
PhyloP100		0.016
Mutation Taster		=100/0	polymorphism (auto)

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: rs2024917; hg19: chrX-37920962;