1-180993146-A-G

Variant names:

• chr1-180993146-A-G
• rs1411478
• NM_005819.6:c.363+217T>C

Variant summary

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

The NM_005819.6(STX6):​c.363+217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,922 control chromosomes in the GnomAD database, including 24,255 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (24255 hom., cov: 31)
• Consequence: STX6 NM_005819.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733
• Publications: 55 publications found

Genes affected

STX6 (HGNC:11441): (syntaxin 6) Enables syntaxin binding activity. Involved in several processes, including Golgi ribbon formation; retrograde transport, endosome to Golgi; and vesicle fusion. Acts upstream of or within endocytic recycling. Located in several cellular components, including early endosome; perinuclear region of cytoplasm; and trans-Golgi network. Part of SNARE complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005819.6. 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
	STX6	NM_005819.6	MANE Select	c.363+217T>C		intron	N/A	NP_005810.1	O43752-1
	STX6	NM_001286210.2		c.60+217T>C		intron	N/A	NP_001273139.1	O43752-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX6	ENST00000258301.6	TSL:1 MANE Select	c.363+217T>C		intron	N/A	ENSP00000258301.5	O43752-1
	STX6	ENST00000542060.5	TSL:2	c.60+217T>C		intron	N/A	ENSP00000440188.1	O43752-2

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85202 AN: 151804 Hom.: 24246 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.532

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.561 AC: 85253 AN: 151922 Hom.: 24255 Cov.: 31 AF XY: 0.563 AC XY: 41808 AN XY: 74242

African (AFR) AF: 0.475 AC: 19673 AN: 41408

American (AMR) AF: 0.607 AC: 9268 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1784 AN: 3472

East Asian (EAS) AF: 0.634 AC: 3269 AN: 5158

South Asian (SAS) AF: 0.437 AC: 2105 AN: 4820

European-Finnish (FIN) AF: 0.663 AC: 6993 AN: 10544

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40193 AN: 67942

Other (OTH) AF: 0.533 AC: 1121 AN: 2104

Alfa AF: 0.580 Hom.: 88531

Bravo AF: 0.557

Asia WGS AF: 0.522 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.63
DANN	Benign	0.77
PhyloP100		-0.73
Mutation Taster		=100/0	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: rs1411478; hg19: chr1-180962282; COSMIC: COSV51113927; COSMIC: COSV51113927;