chrX-38108615-T-C

Variant names:

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

Variant summary

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

The NM_138780.3(SYTL5):​c.1350T>C​(p.Tyr450Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,185,999 control chromosomes in the GnomAD database, including 36,927 homozygotes. There are 101,193 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 0.39 (8631 hom., 12203 hem., cov: 22)
  • Exomes 𝑓: 0.26 (28296 hom. 88990 hem.)
• Consequence: SYTL5 NM_138780.3 synonymous
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL5	NM_138780.3	c.1350T>C	p.Tyr450Tyr	synonymous_variant	Exon 12 of 17	ENST00000297875.7	NP_620135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYTL5	ENST00000297875.7	c.1350T>C	p.Tyr450Tyr	synonymous_variant	Exon 12 of 17	5	NM_138780.3	ENSP00000297875.2
SYTL5	ENST00000456733.2	c.1416T>C	p.Tyr472Tyr	synonymous_variant	Exon 12 of 17	1		ENSP00000395220.2
ENSG00000250349	ENST00000465127.1	c.172-557506T>C		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 43370 AN: 110521 Hom.: 8627 Cov.: 22

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.386

GnomAD2 exomes AF: 0.291 AC: 47191 AN: 162033 AF XY: 0.280

Gnomad AFR exome AF: 0.785

Gnomad AMR exome AF: 0.372

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.104

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.258 AC: 277128 AN: 1075425 Hom.: 28296 Cov.: 26 AF XY: 0.256 AC XY: 88990 AN XY: 347827

African (AFR) AF: 0.791 AC: 20120 AN: 25425

American (AMR) AF: 0.370 AC: 12674 AN: 34295

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 4280 AN: 19194

East Asian (EAS) AF: 0.112 AC: 3299 AN: 29393

South Asian (SAS) AF: 0.348 AC: 18084 AN: 51998

European-Finnish (FIN) AF: 0.140 AC: 5614 AN: 39962

Middle Eastern (MID) AF: 0.337 AC: 1384 AN: 4101

European-Non Finnish (NFE) AF: 0.240 AC: 198501 AN: 825855

Other (OTH) AF: 0.291 AC: 13172 AN: 45202

GnomAD4 genome AF: 0.393 AC: 43411 AN: 110574 Hom.: 8631 Cov.: 22 AF XY: 0.372 AC XY: 12203 AN XY: 32846

African (AFR) AF: 0.769 AC: 23222 AN: 30187

American (AMR) AF: 0.382 AC: 3962 AN: 10372

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 618 AN: 2633

East Asian (EAS) AF: 0.100 AC: 355 AN: 3541

South Asian (SAS) AF: 0.363 AC: 939 AN: 2587

European-Finnish (FIN) AF: 0.124 AC: 737 AN: 5959

Middle Eastern (MID) AF: 0.344 AC: 74 AN: 215

European-Non Finnish (NFE) AF: 0.242 AC: 12781 AN: 52894

Other (OTH) AF: 0.382 AC: 575 AN: 1507

Alfa AF: 0.323 Hom.: 4740

Bravo AF: 0.431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.5
DANN	Benign	0.71
PhyloP100		0.29
Mutation Taster		=98/2	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: rs5918476; hg19: chrX-37967868; COSMIC: COSV52901409;