X-38089579-A-G

Variant names:

• chrX-38089579-A-G
• rs4827331
• NM_138780.3:c.823A>G

Variant summary

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

The NM_138780.3(SYTL5):​c.823A>G​(p.Ile275Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,206,320 control chromosomes in the GnomAD database, including 8,749 homozygotes. There are 55,805 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (794 hom., 4006 hem., cov: 22)
  • Exomes 𝑓: 0.14 (7955 hom. 51799 hem.)
• Consequence: SYTL5 NM_138780.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 15 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 (MetaRNN=0.001370877).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYTL5	NM_138780.3	MANE Select	c.823A>G	p.Ile275Val	missense	Exon 7 of 17	NP_620135.1	Q8TDW5-1
	SYTL5	NM_001163334.1		c.823A>G	p.Ile275Val	missense	Exon 6 of 17	NP_001156806.1	Q8TDW5-2
	SYTL5	NM_001163335.2		c.823A>G	p.Ile275Val	missense	Exon 8 of 18	NP_001156807.1	Q8TDW5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYTL5	ENST00000297875.7	TSL:5 MANE Select	c.823A>G	p.Ile275Val	missense	Exon 7 of 17	ENSP00000297875.2	Q8TDW5-1
	SYTL5	ENST00000456733.2	TSL:1	c.823A>G	p.Ile275Val	missense	Exon 6 of 17	ENSP00000395220.2	Q8TDW5-2
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-576542A>G		intron	N/A	ENSP00000417050.1	B4E171

Frequencies

GnomAD3 genomes AF: 0.131 AC: 14572 AN: 111236 Hom.: 795 Cov.: 22

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0342

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.147

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.120 AC: 21173 AN: 176956 AF XY: 0.124

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.0712

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.0285

Gnomad FIN exome AF: 0.0867

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.144 AC: 157253 AN: 1095030 Hom.: 7955 Cov.: 30 AF XY: 0.144 AC XY: 51799 AN XY: 360830

African (AFR) AF: 0.142 AC: 3721 AN: 26277

American (AMR) AF: 0.0744 AC: 2597 AN: 34918

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 2249 AN: 19263

East Asian (EAS) AF: 0.0259 AC: 778 AN: 30093

South Asian (SAS) AF: 0.132 AC: 7057 AN: 53560

European-Finnish (FIN) AF: 0.0966 AC: 3899 AN: 40383

Middle Eastern (MID) AF: 0.163 AC: 634 AN: 3888

European-Non Finnish (NFE) AF: 0.154 AC: 129808 AN: 840718

Other (OTH) AF: 0.142 AC: 6510 AN: 45930

GnomAD4 genome AF: 0.131 AC: 14573 AN: 111290 Hom.: 794 Cov.: 22 AF XY: 0.119 AC XY: 4006 AN XY: 33528

African (AFR) AF: 0.126 AC: 3840 AN: 30578

American (AMR) AF: 0.101 AC: 1064 AN: 10534

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 310 AN: 2640

East Asian (EAS) AF: 0.0341 AC: 120 AN: 3524

South Asian (SAS) AF: 0.129 AC: 335 AN: 2607

European-Finnish (FIN) AF: 0.0785 AC: 474 AN: 6035

Middle Eastern (MID) AF: 0.157 AC: 34 AN: 217

European-Non Finnish (NFE) AF: 0.153 AC: 8081 AN: 52954

Other (OTH) AF: 0.148 AC: 225 AN: 1523

Alfa AF: 0.143 Hom.: 14197

Bravo AF: 0.134

TwinsUK AF: 0.156 AC: 579

ALSPAC AF: 0.153 AC: 443

ESP6500AA AF: 0.134 AC: 515

ESP6500EA AF: 0.156 AC: 1048

ExAC AF: 0.128 AC: 15493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.95	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.3
DANN	Benign	0.60
DEOGEN2	Benign	0.0050	T
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.0
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.056
Sift	Benign	0.38	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.041
MPC		0.033
ClinPred		0.0038	T
GERP RS		3.9
Varity_R		0.043
gMVP		0.17
Mutation Taster		=99/1	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: rs4827331; hg19: chrX-37948832;