1-155250576-A-T

Variant names:

• chr1-155250576-A-T
• rs964087093
• NM_006589.3:c.1210T>A

Variant summary

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

The NM_006589.3(ENTREP3):​c.1210T>A​(p.Cys404Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,374 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. C404G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ENTREP3 NM_006589.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.50

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.1210T>A	p.Cys404Ser	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.1210T>A	p.Cys404Ser	missense_variant	Exon 9 of 12	1	NM_006589.3	ENSP00000354958.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449374 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 720680

African (AFR) AF: 0.00 AC: 0 AN: 33354

American (AMR) AF: 0.00 AC: 0 AN: 44004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.00 AC: 0 AN: 85408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108238

Other (OTH) AF: 0.00 AC: 0 AN: 59912

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0097	.;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.55	.;.;N
PhyloP100		6.5
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.35	N;N;N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.037	D;D;D
Polyphen		0.96	D;.;P
Vest4		0.70
MutPred		0.31		.;.;Gain of glycosylation at C404 (P = 0.0016);
MVP		0.36
MPC		1.0
ClinPred		0.89	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.54
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

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Other links and lift over

dbSNP: rs964087093; hg19: chr1-155220367;