rs770820768

Variant names:

• chr19-17216320-C-G
• rs770820768
• NM_018467.4:c.383C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-17216320-C-G
• chr19-17216320-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018467.4(USE1):​c.383C>G​(p.Thr128Arg) variant causes a missense, splice region 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. 15/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T128M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USE1 NM_018467.4 missense, splice_region
• Scores: Splicing: ADA: 0.004811
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

Genes affected

USE1 (HGNC:30882): (unconventional SNARE in the ER 1) Predicted to enable SNAP receptor activity. Predicted to be involved in several processes, including lysosomal transport; protein catabolic process; and retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum. Predicted to act upstream of or within endoplasmic reticulum tubular network organization and regulation of ER to Golgi vesicle-mediated transport. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17437926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USE1	NM_018467.4	c.383C>G	p.Thr128Arg	missense_variant, splice_region_variant	Exon 4 of 8	ENST00000263897.10	NP_060937.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USE1	ENST00000263897.10	c.383C>G	p.Thr128Arg	missense_variant, splice_region_variant	Exon 4 of 8	1	NM_018467.4	ENSP00000263897.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T;.;.;T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.71	T;T;T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;M;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.72	N;.;.;N;.
REVEL	Benign	0.12
Sift	Benign	0.13	T;.;.;T;.
Sift4G	Benign	0.080	T;T;D;T;T
Polyphen		0.62	P;P;P;.;.
Vest4		0.34
MutPred		0.33		Loss of phosphorylation at T128 (P = 0.0506);Loss of phosphorylation at T128 (P = 0.0506);Loss of phosphorylation at T128 (P = 0.0506);Loss of phosphorylation at T128 (P = 0.0506);.;
MVP		0.54
MPC		0.41
ClinPred		0.55	D
GERP RS		1.4
Varity_R		0.063
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0048
dbscSNV1_RF	Benign	0.092
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.40		Position offset: -16

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

Publications

LitVar

Other links and lift over

dbSNP: rs770820768; hg19: chr19-17327129;