rs143765985

Variant names:

• chr9-69377439-C-A
• rs143765985
• NM_001347995.2:c.781C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-69377439-C-A
• chr9-69377439-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001347995.2(ENTREP1):​c.781C>A​(p.Arg261Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. R261C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENTREP1 NM_001347995.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99
• Publications: 0 publications found

Genes affected

ENTREP1 (HGNC:24820): (endosomal transmembrane epsin interactor 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENTREP1 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37531123).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347995.2. 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
	ENTREP1	NM_001347995.2	MANE Select	c.781C>A	p.Arg261Ser	missense	Exon 5 of 11	NP_001334924.1	Q15884-4
	ENTREP1	NM_001127608.3		c.322C>A	p.Arg108Ser	missense	Exon 5 of 11	NP_001121080.1	Q15884-3
	ENTREP1	NM_004816.5		c.322C>A	p.Arg108Ser	missense	Exon 5 of 11	NP_004807.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTREP1	ENST00000303068.14	TSL:2 MANE Select	c.781C>A	p.Arg261Ser	missense	Exon 5 of 11	ENSP00000304435.8	Q15884-4
	ENTREP1	ENST00000257515.12	TSL:1	c.322C>A	p.Arg108Ser	missense	Exon 5 of 11	ENSP00000257515.8	Q15884-3
	ENTREP1	ENST00000377216.4	TSL:1	n.322C>A		non_coding_transcript_exon	Exon 5 of 10	ENSP00000366422.4	A0A0A0MRU1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.50	N
REVEL	Uncertain	0.31
Sift	Benign	0.51	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.82
MutPred		0.64		Loss of helix (P = 0.1299)
MVP		0.63
MPC		0.75
ClinPred		0.93	D
GERP RS		5.6
Varity_R		0.42
gMVP		0.82
Mutation Taster		=246/54	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs143765985; hg19: chr9-71992355;