rs770978543

Variant names:

• chr9-136407167-G-A
• rs770978543
• NM_001039707.2:c.797C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001039707.2(ENTR1):​c.797C>T​(p.Thr266Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000399 in 1,604,270 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000042 (1 hom.)
• Consequence: ENTR1 NM_001039707.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19135237).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039707.2. 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
	ENTR1	NM_001039707.2	MANE Select	c.797C>T	p.Thr266Met	missense	Exon 5 of 10	NP_001034796.1	Q96C92-1
	ENTR1	NM_006643.4		c.728C>T	p.Thr243Met	missense	Exon 4 of 9	NP_006634.3
	ENTR1	NM_001039708.2		c.578C>T	p.Thr193Met	missense	Exon 3 of 8	NP_001034797.1	Q96C92-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTR1	ENST00000357365.8	TSL:5 MANE Select	c.797C>T	p.Thr266Met	missense	Exon 5 of 10	ENSP00000349929.3	Q96C92-1
	ENTR1	ENST00000298537.11	TSL:1	c.728C>T	p.Thr243Met	missense	Exon 4 of 9	ENSP00000298537.7	Q96C92-2
	ENTR1	ENST00000918209.1		c.1013C>T	p.Thr338Met	missense	Exon 5 of 10	ENSP00000588268.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152240 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000324 AC: 8 AN: 247116 AF XY: 0.0000596

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000420 AC: 61 AN: 1452030 Hom.: 1 Cov.: 50 AF XY: 0.0000513 AC XY: 37 AN XY: 720588

African (AFR) AF: 0.0000301 AC: 1 AN: 33272

American (AMR) AF: 0.0000450 AC: 2 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25964

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39452

South Asian (SAS) AF: 0.000233 AC: 20 AN: 85940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4998

European-Non Finnish (NFE) AF: 0.0000289 AC: 32 AN: 1105534

Other (OTH) AF: 0.0000669 AC: 4 AN: 59782

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152240 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74386

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.92	T
PhyloP100		3.8
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.058
Sift	Benign	0.043	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.97	D
Vest4		0.50
MutPred		0.14		Gain of MoRF binding (P = 0.0737)
MVP		0.51
MPC		0.050
ClinPred		0.12	T
GERP RS		5.4
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.036
gMVP		0.32
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs770978543; hg19: chr9-139301619;