chr9-69377371-A-T

Position:

• chr9-69377371-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001347995.2(ENTREP1):​c.713A>T​(p.Lys238Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENTREP1 NM_001347995.2 missense, splice_region
• Scores: Splicing: ADA: 0.7657
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.97

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTREP1	NM_001347995.2	c.713A>T	p.Lys238Ile	missense_variant, splice_region_variant	5/11	ENST00000303068.14	NP_001334924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENTREP1	ENST00000303068.14	c.713A>T	p.Lys238Ile	missense_variant, splice_region_variant	5/11	2	NM_001347995.2	ENSP00000304435.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.254A>T (p.K85I) alteration is located in exon 5 (coding exon 4) of the FAM189A2 gene. This alteration results from a A to T substitution at nucleotide position 254, causing the lysine (K) at amino acid position 85 to be replaced by an isoleucine (I). 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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.2	D;.;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0090	D;.;D
Sift4G	Uncertain	0.0040	D;.;D
Polyphen		1.0	D;.;D
Vest4		0.81
MutPred		0.49		Loss of ubiquitination at K85 (P = 0.0297);.;Loss of ubiquitination at K85 (P = 0.0297);
MVP		0.50
MPC		0.97
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.44
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.77
dbscSNV1_RF	Pathogenic	0.76
SpliceAI score (max)		0.19		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

Other links and lift over

dbSNP: rs1342551192; hg19: chr9-71992287;