chr9-136402806-G-C

Variant names:

• chr9-136402806-G-C
• rs372063103
• NM_001039707.2:c.1290C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001039707.2(ENTR1):​c.1290C>G​(p.Asp430Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ENTR1 NM_001039707.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -8.40
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032844037).
• BP6: Variant 9-136402806-G-C is Benign according to our data. Variant chr9-136402806-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 4018275.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTR1	NM_001039707.2	c.1290C>G	p.Asp430Glu	missense_variant	Exon 10 of 10	ENST00000357365.8	NP_001034796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTR1	ENST00000357365.8	c.1290C>G	p.Asp430Glu	missense_variant	Exon 10 of 10	5	NM_001039707.2	ENSP00000349929.3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151928 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000484

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248252 AF XY: 0.00000741

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: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460636 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726626

African (AFR) AF: 0.0000598 AC: 2 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111520

Other (OTH) AF: 0.0000331 AC: 2 AN: 60340

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151928 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74222

African (AFR) AF: 0.0000484 AC: 2 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15240

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000828 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 22, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.0010
DANN	Benign	0.64
DEOGEN2	Benign	0.0048	T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.62	T;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.033	T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-8.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.89	N;N;N
REVEL	Benign	0.039
Sift	Benign	0.32	T;T;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.016	B;B;B
Vest4		0.075
MutPred		0.16		Gain of methylation at K429 (P = 0.1224);.;.;
MVP		0.15
MPC		0.017
ClinPred		0.095	T
GERP RS		-6.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.022
gMVP		0.079
Mutation Taster		=96/4	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: rs372063103; hg19: chr9-139297258;