rs142164979

Variant names:

• chr1-114097771-C-T
• rs142164979
• NM_001253772.2:c.1471G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001253772.2(SYT6):​c.1471G>A​(p.Ala491Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000322 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: SYT6 NM_001253772.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.13
• Publications: 6 publications found

Genes affected

SYT6 (HGNC:18638): (synaptotagmin 6) The protein encoded by this gene belongs to the synaptotagmin family. Synaptotagmins share a common domain structure that includes a transmembrane domain and a cytoplasmic region composed of 2 C2 domains, and are involved in calcium-dependent exocytosis of synaptic vesicles. This protein has been shown to be a key component of the secretory machinery involved in acrosomal exocytosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12876841).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253772.2. 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
	SYT6	NM_001253772.2	MANE Select	c.1471G>A	p.Ala491Thr	missense	Exon 6 of 8	NP_001240701.1
	SYT6	NM_001366224.1		c.1471G>A	p.Ala491Thr	missense	Exon 6 of 7	NP_001353153.1
	SYT6	NM_001366225.1		c.1471G>A	p.Ala491Thr	missense	Exon 6 of 8	NP_001353154.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT6	ENST00000610222.3	TSL:5 MANE Select	c.1471G>A	p.Ala491Thr	missense	Exon 6 of 8	ENSP00000476396.1
	SYT6	ENST00000369547.6	TSL:1	c.1471G>A	p.Ala491Thr	missense	Exon 6 of 7	ENSP00000358560.2
	SYT6	ENST00000610096.1	TSL:1	n.*1172G>A		non_coding_transcript_exon	Exon 6 of 8	ENSP00000477325.1

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000310 AC: 78 AN: 251412 AF XY: 0.000353

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000413

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000325 AC: 475 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.000352 AC XY: 256 AN XY: 727242

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.000246 AC: 11 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000684 AC: 59 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.000324 AC: 360 AN: 1112000

Other (OTH) AF: 0.000414 AC: 25 AN: 60396

GnomAD4 genome AF: 0.000296 AC: 45 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.000323 AC XY: 24 AN XY: 74364

African (AFR) AF: 0.000241 AC: 10 AN: 41446

American (AMR) AF: 0.000654 AC: 10 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68042

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000461 Hom.: 0

Bravo AF: 0.000283

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000305 AC: 37

EpiCase AF: 0.000763

EpiControl AF: 0.000948

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Breast ductal adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.1
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.20
Sift	Benign	0.16	T
Sift4G	Benign	0.14	T
Polyphen		0.39	B
Vest4		0.44
MVP		0.76
MPC		0.11
ClinPred		0.033	T
GERP RS		5.4
Varity_R		0.22
gMVP		0.57
Mutation Taster		=68/32	polymorphism

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: rs142164979; hg19: chr1-114640393;