chr9-136407414-A-C

Variant names:

• chr9-136407414-A-C
• rs1477002688
• NM_001039707.2:c.550T>G

Variant summary

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

The NM_001039707.2(ENTR1):​c.550T>G​(p.Trp184Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ENTR1 NM_001039707.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52
• Publications: 0 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: 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
ENTR1	NM_001039707.2	c.550T>G	p.Trp184Gly	missense_variant	Exon 5 of 10	ENST00000357365.8	NP_001034796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTR1	ENST00000357365.8	c.550T>G	p.Trp184Gly	missense_variant	Exon 5 of 10	5	NM_001039707.2	ENSP00000349929.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.550T>G (p.W184G) alteration is located in exon 5 (coding exon 5) of the SDCCAG3 gene. This alteration results from a T to G substitution at nucleotide position 550, causing the tryptophan (W) at amino acid position 184 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	0.32
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Benign	0.16	T;.;.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.66	D;D;D;D
MetaSVM	Benign	-0.46	T
PhyloP100		5.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.8	D;D;D;D
REVEL	Uncertain	0.32
Sift	Benign	0.038	D;T;T;D
Sift4G	Benign	0.10	T;T;T;D
Polyphen		1.0	D;D;D;.
Vest4		0.71
MutPred		0.51		Gain of disorder (P = 0.0067);.;.;.;
MVP		0.71
MPC		0.14
ClinPred		0.98	D
GERP RS		5.2
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.45
gMVP		0.24
Mutation Taster		=66/34	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: rs1477002688; hg19: chr9-139301866;