1-155250371-G-T

Variant names:

• chr1-155250371-G-T
• rs1000466806
• NM_006589.3:c.1415C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006589.3(ENTREP3):​c.1415C>A​(p.Pro472Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,393,094 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. P472L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: ENTREP3 NM_006589.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21531624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTREP3	NM_006589.3	c.1415C>A	p.Pro472Gln	missense_variant	Exon 9 of 12	ENST00000361361.7	NP_006580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTREP3	ENST00000361361.7	c.1415C>A	p.Pro472Gln	missense_variant	Exon 9 of 12	1	NM_006589.3	ENSP00000354958.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000697 AC: 1 AN: 143460 AF XY: 0.0000131

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000193

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000230 AC: 32 AN: 1393094 Hom.: 0 Cov.: 33 AF XY: 0.0000131 AC XY: 9 AN XY: 687228

African (AFR) AF: 0.00 AC: 0 AN: 31096

American (AMR) AF: 0.00 AC: 0 AN: 35326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24926

East Asian (EAS) AF: 0.00 AC: 0 AN: 35328

South Asian (SAS) AF: 0.00 AC: 0 AN: 78898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4100

European-Non Finnish (NFE) AF: 0.0000297 AC: 32 AN: 1077392

Other (OTH) AF: 0.00 AC: 0 AN: 57622

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	.;.;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.52	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.55	.;.;N
PhyloP100		3.5
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.51	N;N;N
REVEL	Benign	0.076
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.33
MutPred		0.21		.;.;Loss of catalytic residue at P472 (P = 0.0094);
MVP		0.44
MPC		2.7
ClinPred		0.68	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.34
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1000466806; hg19: chr1-155220162;