NM_138780.3:c.489A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_138780.3(SYTL5):​c.489A>G​(p.Ala163Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,195,168 control chromosomes in the GnomAD database, including 27,479 homozygotes. There are 97,531 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 (3865 hom., 9223 hem., cov: 22)
  • Exomes 𝑓: 0.25 (23614 hom. 88308 hem.)
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.198 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.292 AC: 32276 AN: 110620 Hom.: 3865 Cov.: 22

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0951

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.311

GnomAD2 exomes AF: 0.245 AC: 38576 AN: 157759 AF XY: 0.222

Gnomad AFR exome AF: 0.412

Gnomad AMR exome AF: 0.335

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.0939

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.265

GnomAD4 exome AF: 0.248 AC: 269093 AN: 1084491 Hom.: 23614 Cov.: 29 AF XY: 0.249 AC XY: 88308 AN XY: 354113

African (AFR) AF: 0.436 AC: 11386 AN: 26123

American (AMR) AF: 0.338 AC: 11187 AN: 33101

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 4243 AN: 19092

East Asian (EAS) AF: 0.109 AC: 3248 AN: 29888

South Asian (SAS) AF: 0.351 AC: 18130 AN: 51582

European-Finnish (FIN) AF: 0.139 AC: 5527 AN: 39782

Middle Eastern (MID) AF: 0.326 AC: 1324 AN: 4063

European-Non Finnish (NFE) AF: 0.242 AC: 201791 AN: 835219

Other (OTH) AF: 0.269 AC: 12257 AN: 45641

GnomAD4 genome AF: 0.292 AC: 32294 AN: 110677 Hom.: 3865 Cov.: 22 AF XY: 0.280 AC XY: 9223 AN XY: 32977

African (AFR) AF: 0.416 AC: 12620 AN: 30323

American (AMR) AF: 0.345 AC: 3572 AN: 10365

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 620 AN: 2637

East Asian (EAS) AF: 0.0945 AC: 332 AN: 3514

South Asian (SAS) AF: 0.368 AC: 958 AN: 2603

European-Finnish (FIN) AF: 0.123 AC: 731 AN: 5957

Middle Eastern (MID) AF: 0.327 AC: 69 AN: 211

European-Non Finnish (NFE) AF: 0.242 AC: 12782 AN: 52876

Other (OTH) AF: 0.307 AC: 465 AN: 1514

Alfa AF: 0.274 Hom.: 5268

Bravo AF: 0.316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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; COSMIC: COSV52901394;