X-38089579-A-G

Position:

• chrX-38089579-A-G

Variant summary

Our verdict is Benign. Variant got -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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYTL5	NM_138780.3	c.823A>G	p.Ile275Val	missense_variant	7/17	ENST00000297875.7	NP_620135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYTL5	ENST00000297875.7	c.823A>G	p.Ile275Val	missense_variant	7/17	5	NM_138780.3	ENSP00000297875	P4
SYTL5	ENST00000456733.2	c.823A>G	p.Ile275Val	missense_variant	6/17	1		ENSP00000395220	A1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 14572 AN: 111236 Hom.: 795 Cov.: 22 AF XY: 0.120 AC XY: 4003 AN XY: 33464

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

GnomAD3 exomes AF: 0.120 AC: 21173 AN: 176956 Hom.: 962 AF XY: 0.124 AC XY: 7698 AN XY: 62292

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 SAS exome AF: 0.136

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

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.0744

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.0259

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.0966

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.142

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

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0341

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0785

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.148

Alfa AF: 0.144 Hom.: 12343

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 v4.3

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;T
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.0	N;N
REVEL	Benign	0.056
Sift	Benign	0.38	T;T
Sift4G	Benign	0.62	T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4827331; hg19: chrX-37948832;