11-85725457-T-C

Variant names:

• chr11-85725457-T-C
• rs580459
• NM_206927.4:c.3901A>G

Variant summary

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

The NM_206927.4(SYTL2):​c.3901A>G​(p.Met1301Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 1,613,818 control chromosomes in the GnomAD database, including 355,306 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 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 0.70 (38235 hom., cov: 32)
  • Exomes 𝑓: 0.66 (317071 hom.)
• Consequence: SYTL2 NM_206927.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 35 publications found

Genes affected

SYTL2 (HGNC:15585): (synaptotagmin like 2) The protein encoded by this gene is a synaptotagmin-like protein (SLP) that belongs to a C2 domain-containing protein family. The SLP homology domain (SHD) of this protein has been shown to specifically bind the GTP-bound form of Ras-related protein Rab-27A (RAB27A). This protein plays a role in RAB27A-dependent vesicle trafficking and controls melanosome distribution in the cell periphery. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jun 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.3917257E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206927.4. 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
	SYTL2	NM_206927.4	MANE Select	c.3901A>G	p.Met1301Val	missense	Exon 8 of 20	NP_996810.2
	SYTL2	NM_001394447.1		c.3898A>G	p.Met1300Val	missense	Exon 8 of 20	NP_001381376.1
	SYTL2	NM_001394448.1		c.3901A>G	p.Met1301Val	missense	Exon 8 of 19	NP_001381377.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYTL2	ENST00000359152.10	TSL:1 MANE Select	c.3901A>G	p.Met1301Val	missense	Exon 8 of 20	ENSP00000352065.7
	SYTL2	ENST00000525423.5	TSL:1	n.2572A>G		non_coding_transcript_exon	Exon 1 of 12
	SYTL2	ENST00000528231.5	TSL:1	c.1459+2439A>G		intron	N/A	ENSP00000431701.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106884 AN: 151984 Hom.: 38204 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.668

GnomAD2 exomes AF: 0.648 AC: 162772 AN: 251148 AF XY: 0.643

Gnomad AFR exome AF: 0.836

Gnomad AMR exome AF: 0.573

Gnomad ASJ exome AF: 0.663

Gnomad EAS exome AF: 0.605

Gnomad FIN exome AF: 0.712

Gnomad NFE exome AF: 0.666

Gnomad OTH exome AF: 0.633

GnomAD4 exome AF: 0.656 AC: 959141 AN: 1461716 Hom.: 317071 Cov.: 59 AF XY: 0.652 AC XY: 474335 AN XY: 727168

African (AFR) AF: 0.840 AC: 28132 AN: 33480

American (AMR) AF: 0.576 AC: 25742 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 17362 AN: 26130

East Asian (EAS) AF: 0.582 AC: 23115 AN: 39700

South Asian (SAS) AF: 0.548 AC: 47306 AN: 86248

European-Finnish (FIN) AF: 0.708 AC: 37759 AN: 53330

Middle Eastern (MID) AF: 0.652 AC: 3759 AN: 5768

European-Non Finnish (NFE) AF: 0.662 AC: 736201 AN: 1111952

Other (OTH) AF: 0.658 AC: 39765 AN: 60388

GnomAD4 genome AF: 0.703 AC: 106967 AN: 152102 Hom.: 38235 Cov.: 32 AF XY: 0.703 AC XY: 52242 AN XY: 74336

African (AFR) AF: 0.832 AC: 34560 AN: 41526

American (AMR) AF: 0.627 AC: 9587 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2318 AN: 3470

East Asian (EAS) AF: 0.590 AC: 3050 AN: 5166

South Asian (SAS) AF: 0.536 AC: 2580 AN: 4810

European-Finnish (FIN) AF: 0.718 AC: 7577 AN: 10556

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.665 AC: 45203 AN: 67972

Other (OTH) AF: 0.667 AC: 1411 AN: 2114

Alfa AF: 0.670 Hom.: 116404

Bravo AF: 0.699

TwinsUK AF: 0.667 AC: 2473

ALSPAC AF: 0.677 AC: 2608

ESP6500AA AF: 0.824 AC: 3631

ESP6500EA AF: 0.657 AC: 5650

ExAC AF: 0.654 AC: 79459

Asia WGS AF: 0.572 AC: 1985 AN: 3478

EpiCase AF: 0.663

EpiControl AF: 0.647

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.25
DANN	Benign	0.81
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	8.4e-7	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.8
PrimateAI	Benign	0.24	T
REVEL	Benign	0.016
Sift4G	Benign	0.62	T
Vest4		0.048
MPC		0.013
GERP RS		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs580459; hg19: chr11-85436500; COSMIC: COSV60364949; COSMIC: COSV60364949;