15-29124717-C-T

Position:

• chr15-29124717-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015307.2(ENTREP2):​c.1273G>A​(p.Ala425Thr) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ENTREP2 NM_015307.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20

Genes affected

ENTREP2 (HGNC:29075): (endosomal transmembrane epsin interactor 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046307534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENTREP2	NM_015307.2	c.1273G>A	p.Ala425Thr	missense_variant	10/11	ENST00000261275.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENTREP2	ENST00000261275.5	c.1273G>A	p.Ala425Thr	missense_variant	10/11	5	NM_015307.2	P1
ENTREP2	ENST00000560021.1	n.1009G>A		non_coding_transcript_exon_variant	7/8	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 06, 2021

The c.1273G>A (p.A425T) alteration is located in exon 10 (coding exon 10) of the FAM189A1 gene. This alteration results from a G to A substitution at nucleotide position 1273, causing the alanine (A) at amino acid position 425 to be replaced by a threonine (T). 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	0.072
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.2
DANN	Benign	0.92
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.071
Sift	Benign	0.22	T
Sift4G	Benign	0.26	T
Polyphen		0.20	B
Vest4		0.051
MutPred		0.061		Loss of helix (P = 0.079);
MVP		0.030
ClinPred		0.19	T
GERP RS		1.7
Varity_R		0.030
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-29416920;