NM_006589.3:c.1949G>C

Variant names:

• chr1-155247840-C-G
• rs572393078
• NM_006589.3:c.1949G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006589.3(ENTREP3):​c.1949G>C​(p.Arg650Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000872 in 1,490,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. R650H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: ENTREP3 NM_006589.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05754432).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006589.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTREP3	NM_006589.3	MANE Select	c.1949G>C	p.Arg650Pro	missense	Exon 12 of 12	NP_006580.2
	ENTREP3	NM_001267608.2		c.1895G>C	p.Arg632Pro	missense	Exon 11 of 11	NP_001254537.1	P81408-3
	ENTREP3	NM_198264.2		c.1661G>C	p.Arg554Pro	missense	Exon 9 of 9	NP_937995.1	P81408-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTREP3	ENST00000361361.7	TSL:1 MANE Select	c.1949G>C	p.Arg650Pro	missense	Exon 12 of 12	ENSP00000354958.2	P81408-1
	ENTREP3	ENST00000368368.7	TSL:1	c.1895G>C	p.Arg632Pro	missense	Exon 11 of 11	ENSP00000357352.3	P81408-3
	ENTREP3	ENST00000350210.6	TSL:1	c.1661G>C	p.Arg554Pro	missense	Exon 9 of 9	ENSP00000307128.4	P81408-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152232 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000920 AC: 1 AN: 108686 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000651

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000897 AC: 12 AN: 1338414 Hom.: 0 Cov.: 32 AF XY: 0.00000764 AC XY: 5 AN XY: 654036

African (AFR) AF: 0.00 AC: 0 AN: 29758

American (AMR) AF: 0.0000402 AC: 1 AN: 24864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20184

East Asian (EAS) AF: 0.00 AC: 0 AN: 36590

South Asian (SAS) AF: 0.00 AC: 0 AN: 68002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4842

European-Non Finnish (NFE) AF: 0.00000950 AC: 10 AN: 1052098

Other (OTH) AF: 0.0000181 AC: 1 AN: 55182

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152232 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.0091	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.30	N
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.061
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.14
Sift	Benign	0.051	T
Sift4G	Uncertain	0.011	D
Polyphen		0.012	B
Vest4		0.20
MutPred		0.17		Loss of MoRF binding (P = 0.0025)
MVP		0.14
MPC		0.12
ClinPred		0.044	T
GERP RS		1.6
Varity_R		0.13
gMVP		0.33
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs572393078; hg19: chr1-155217631;