NM_145003.5:c.*11+1330G>T

Variant names:

• chr8-142228143-C-A
• rs10098073
• NM_145003.5:c.*11+1330G>T

Variant summary

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

The NM_145003.5(TSNARE1):​c.*11+1330G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,136 control chromosomes in the GnomAD database, including 11,163 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 0.35 (11163 hom., cov: 33)
• Consequence: TSNARE1 NM_145003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 13 publications found

Genes affected

TSNARE1 (HGNC:26437): (t-SNARE domain containing 1) Predicted to enable SNAP receptor activity and SNARE binding activity. Predicted to be involved in intracellular protein transport; vesicle docking; and vesicle fusion. Predicted to be located in membrane. Predicted to be part of SNARE complex. Predicted to be active in endomembrane system. Predicted to be integral component of membrane. [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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSNARE1	NM_145003.5	c.*11+1330G>T		intron_variant	Intron 13 of 13	ENST00000524325.6	NP_659440.2
TSNARE1	NM_001363740.2	c.*11+1330G>T		intron_variant	Intron 13 of 13		NP_001350669.1
TSNARE1	NM_001366901.1	c.*11+1330G>T		intron_variant	Intron 13 of 13		NP_001353830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSNARE1	ENST00000524325.6	c.*11+1330G>T		intron_variant	Intron 13 of 13	2	NM_145003.5	ENSP00000428763.2
TSNARE1	ENST00000520166.5	c.*11+1330G>T		intron_variant	Intron 12 of 12	1		ENSP00000427770.2
TSNARE1	ENST00000662555.2	c.*11+1330G>T		intron_variant	Intron 13 of 13			ENSP00000499343.2
TSNARE1	ENST00000307180.4	c.*11+1330G>T		intron_variant	Intron 13 of 13	5		ENSP00000303437.4

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53698 AN: 152016 Hom.: 11165 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.346

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.353 AC: 53704 AN: 152136 Hom.: 11163 Cov.: 33 AF XY: 0.349 AC XY: 25965 AN XY: 74386

African (AFR) AF: 0.145 AC: 6024 AN: 41528

American (AMR) AF: 0.316 AC: 4838 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1499 AN: 3468

East Asian (EAS) AF: 0.262 AC: 1350 AN: 5160

South Asian (SAS) AF: 0.238 AC: 1151 AN: 4828

European-Finnish (FIN) AF: 0.451 AC: 4773 AN: 10578

Middle Eastern (MID) AF: 0.352 AC: 102 AN: 290

European-Non Finnish (NFE) AF: 0.482 AC: 32784 AN: 67968

Other (OTH) AF: 0.373 AC: 787 AN: 2110

Alfa AF: 0.428 Hom.: 14862

Bravo AF: 0.337

Asia WGS AF: 0.266 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.74
PhyloP100		0.11
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: rs10098073; hg19: chr8-143309504;