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GeneBe

9-136407305-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039707.2(ENTR1):c.659A>G(p.Glu220Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,611,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ENTR1
NM_001039707.2 missense

Scores

5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31
Variant links:
Genes affected
ENTR1 (HGNC:10667): (endosome associated trafficking regulator 1) Involved in several processes, including endocytic recycling; positive regulation of cilium assembly; and positive regulation of protein localization to cilium. Located in endosome; microtubule organizing center; and midbody. Colocalizes with retromer complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

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=0.14243308).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ENTR1NM_001039707.2 linkuse as main transcriptc.659A>G p.Glu220Gly missense_variant 5/10 ENST00000357365.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ENTR1ENST00000357365.8 linkuse as main transcriptc.659A>G p.Glu220Gly missense_variant 5/105 NM_001039707.2 A1Q96C92-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151886
Hom.:
0
Cov.:
31
show subpopulations
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:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000244
AC:
6
AN:
245672
Hom.:
0
AF XY:
0.0000373
AC XY:
5
AN XY:
133896
show subpopulations
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 SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000902
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1459718
Hom.:
0
Cov.:
49
AF XY:
0.0000289
AC XY:
21
AN XY:
726118
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000244
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151886
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74152
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000827
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 28, 2023The c.659A>G (p.E220G) alteration is located in exon 5 (coding exon 5) of the SDCCAG3 gene. This alteration results from a A to G substitution at nucleotide position 659, causing the glutamic acid (E) at amino acid position 220 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.39
Cadd
Benign
18
Dann
Uncertain
1.0
DEOGEN2
Benign
0.042
T;.;.;T
Eigen
Benign
-0.077
Eigen_PC
Benign
-0.0048
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.87
D;D;D;D
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-0.86
T
MutationTaster
Benign
0.75
D;D;D
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-2.3
N;N;N;D
REVEL
Benign
0.070
Sift
Uncertain
0.013
D;D;T;D
Sift4G
Uncertain
0.024
D;D;D;D
Polyphen
0.42
B;B;B;.
Vest4
0.20
MutPred
0.15
Gain of glycosylation at S219 (P = 0.042);.;.;.;
MVP
0.49
MPC
0.030
ClinPred
0.098
T
GERP RS
5.3
Varity_R
0.094
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs754705615; hg19: chr9-139301757; API