8-142231572-A-G

Variant names:

• chr8-142231572-A-G
• rs4129585
• NM_145003.5:c.1447-1993T>C

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 75 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: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145003.5. 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
	TSNARE1	NM_145003.5	MANE Select	c.1447-1993T>C		intron	N/A	NP_659440.2	Q96NA8-1
	TSNARE1	NM_001363740.2		c.1450-1993T>C		intron	N/A	NP_001350669.1	A0AVG3
	TSNARE1	NM_001366901.1		c.1444-1993T>C		intron	N/A	NP_001353830.1	Q96NA8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSNARE1	ENST00000524325.6	TSL:2 MANE Select	c.1447-1993T>C		intron	N/A	ENSP00000428763.2	Q96NA8-1
	TSNARE1	ENST00000520166.5	TSL:1	c.1450-1993T>C		intron	N/A	ENSP00000427770.2	A0AVG3
	TSNARE1	ENST00000662555.2		c.1915-1993T>C		intron	N/A	ENSP00000499343.2	A0A590UJA6

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.5
DANN	Benign	0.77
PhyloP100		-0.056

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: rs4129585; hg19: chr8-143312933;