19-17217457-C-T

Variant names:

• chr19-17217457-C-T
• rs1006849955
• NM_018467.4:c.389C>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.389C>T​(p.Ser130Phe) variant causes a missense 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. 15/21 in silico tools predict 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: 30)
• Consequence: USE1 NM_018467.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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=0.08441228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USE1	NM_018467.4	c.389C>T	p.Ser130Phe	missense_variant	Exon 5 of 8	ENST00000263897.10	NP_060937.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USE1	ENST00000263897.10	c.389C>T	p.Ser130Phe	missense_variant	Exon 5 of 8	1	NM_018467.4	ENSP00000263897.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.17	T;.;.;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.38	T;T;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.084	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;L;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.1	N;.;.;.
REVEL	Benign	0.018
Sift	Uncertain	0.029	D;.;.;.
Sift4G	Benign	0.070	T;T;D;D
Polyphen		0.24	B;B;P;.
Vest4		0.17
MutPred		0.35		Loss of phosphorylation at S130 (P = 0.0167);Loss of phosphorylation at S130 (P = 0.0167);Loss of phosphorylation at S130 (P = 0.0167);.;
MVP		0.29
MPC		0.37
ClinPred		0.18	T
GERP RS		0.037
Varity_R		0.053
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1006849955; hg19: chr19-17328266;