chrX-38089579-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000297875.7(SYTL5):​c.823A>C​(p.Ile275Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,206,467 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.0000090 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: SYTL5 ENST00000297875.7 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07240504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000297875.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYTL5	NM_138780.3	MANE Select	c.823A>C	p.Ile275Leu	missense	Exon 7 of 17	NP_620135.1
	SYTL5	NM_001163334.1		c.823A>C	p.Ile275Leu	missense	Exon 6 of 17	NP_001156806.1
	SYTL5	NM_001163335.2		c.823A>C	p.Ile275Leu	missense	Exon 8 of 18	NP_001156807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYTL5	ENST00000297875.7	TSL:5 MANE Select	c.823A>C	p.Ile275Leu	missense	Exon 7 of 17	ENSP00000297875.2
	SYTL5	ENST00000456733.2	TSL:1	c.823A>C	p.Ile275Leu	missense	Exon 6 of 17	ENSP00000395220.2
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-576542A>C		intron	N/A	ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.00000899 AC: 1 AN: 111276 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000950

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000113 AC: 2 AN: 176956 AF XY: 0.0000161

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000745

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1095191 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 1 AN XY: 360919

African (AFR) AF: 0.00 AC: 0 AN: 26277

American (AMR) AF: 0.0000573 AC: 2 AN: 34928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19265

East Asian (EAS) AF: 0.00 AC: 0 AN: 30093

South Asian (SAS) AF: 0.00 AC: 0 AN: 53563

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40397

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3894

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840838

Other (OTH) AF: 0.00 AC: 0 AN: 45936

GnomAD4 genome AF: 0.00000899 AC: 1 AN: 111276 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33484

African (AFR) AF: 0.00 AC: 0 AN: 30522

American (AMR) AF: 0.0000950 AC: 1 AN: 10525

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3535

South Asian (SAS) AF: 0.00 AC: 0 AN: 2615

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6039

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52978

Other (OTH) AF: 0.00 AC: 0 AN: 1504

Alfa AF: 0.00 Hom.: 14197

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.7
DANN	Benign	0.64
DEOGEN2	Benign	0.0050	T
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.0
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.040
Sift	Benign	0.44	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.094
MutPred		0.13		Gain of phosphorylation at T272 (P = 0.0959)
MVP		0.21
MPC		0.036
ClinPred		0.028	T
GERP RS		3.9
Varity_R		0.093
gMVP		0.18
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;