1-155248114-C-A

Variant names:

• chr1-155248114-C-A
• rs201013021
• NM_006589.3:c.1769G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006589.3(ENTREP3):​c.1769G>T​(p.Arg590Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R590H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ENTREP3 NM_006589.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 3 publications found

Genes affected

ENTREP3 (HGNC:1233): (endosomal transmembrane epsin interactor 3) This gene is located near the gene for the lysosomal enzyme glucosylceramidase; a deficiency in this enzyme is associated with Gaucher disease. The encoded protein has been identified as a potential binding partner of a WW domain-containing protein which is involved in apoptosis and tumor suppression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
ENTREP3	NM_006589.3	c.1769G>T	p.Arg590Leu	missense_variant	Exon 11 of 12	ENST00000361361.7	NP_006580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTREP3	ENST00000361361.7	c.1769G>T	p.Arg590Leu	missense_variant	Exon 11 of 12	1	NM_006589.3	ENSP00000354958.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152250 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152368 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74504

African (AFR) AF: 0.00 AC: 0 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	.;.;T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.0	.;.;L;.
PhyloP100		3.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.3	N;N;N;N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.94	P;.;D;.
Vest4		0.79
MVP		0.33
MPC		0.14
ClinPred		0.84	D
GERP RS		4.4
Varity_R		0.37
gMVP		0.45
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -11

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

Other links and lift over

dbSNP: rs201013021; hg19: chr1-155217905;