8-142231572-A-G

Position:

• chr8-142231572-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145003.5(TSNARE1):​c.1447-1993T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TSNARE1 NM_145003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSNARE1	NM_145003.5	c.1447-1993T>C		intron_variant		ENST00000524325.6	NP_659440.2
TSNARE1	NM_001363740.2	c.1450-1993T>C		intron_variant			NP_001350669.1
TSNARE1	NM_001366901.1	c.1444-1993T>C		intron_variant			NP_001353830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSNARE1	ENST00000524325.6	c.1447-1993T>C		intron_variant		2	NM_145003.5	ENSP00000428763	A2
TSNARE1	ENST00000520166.5	c.1450-1993T>C		intron_variant		1		ENSP00000427770	P2
TSNARE1	ENST00000307180.4	c.1450-1993T>C		intron_variant		5		ENSP00000303437	P2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.5
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs4129585; hg19: chr8-143312933;