19-12747590-C-T

Variant names:

• chr19-12747590-C-T
• NM_004317.4:c.913C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004317.4(GET3):​c.913C>T​(p.Gln305*) variant causes a stop gained, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GET3 NM_004317.4 stop_gained, splice_region
• Scores: Splicing: ADA: 0.9997
• Clinical Significance: no classification for the single variant no classification for the single variant P:1
• Conservation: PhyloP100: 7.28

Genes affected

GET3 (HGNC:752): (guided entry of tail-anchored proteins factor 3, ATPase) This gene represents the human homolog of the bacterial arsA gene, encoding the arsenite-stimulated ATPase component of the arsenite transporter responsible for resistance to arsenicals. This protein is also a central component of a transmembrane domain (TMD) recognition complex (TRC) that is involved in the post-translational delivery of tail-anchored (TA) proteins from the cytosol to the endoplasmic reticulum (ER). It recognizes and selectively binds the TMD of TA proteins in the cytosol, and delivers them to the ER for insertion. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GET3	NM_004317.4	c.913C>T	p.Gln305*	stop_gained, splice_region_variant	Exon 6 of 7	ENST00000357332.8	NP_004308.2
GET3	NM_001371488.1	c.913C>T	p.Gln305*	stop_gained, splice_region_variant	Exon 7 of 8		NP_001358417.1
GET3	NM_001371489.1	c.913C>T	p.Gln305*	stop_gained, splice_region_variant	Exon 7 of 8		NP_001358418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GET3	ENST00000357332.8	c.913C>T	p.Gln305*	stop_gained, splice_region_variant	Exon 6 of 7	1	NM_004317.4	ENSP00000349887.3
GET3	ENST00000591090.5	c.913C>T	p.Gln305*	stop_gained, splice_region_variant	Exon 7 of 8	5		ENSP00000466379.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: no classification for the single variant

Submissions summary: Pathogenic:1

Revision: no classification for the single variant

Submissions by phenotype

Cardiomyopathy, dilated, 2H Pathogenic:1

Mar 08, 2023

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	48
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.99
FATHMM_MKL	Pathogenic	0.98	D
Vest4		0.85
GERP RS		5.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.96
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.30		Position offset: -11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-12858404;