5-112921232-T-A

Position:

• chr5-112921232-T-A

Variant summary

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

The ENST00000379638.9(REEP5):​c.143A>T​(p.Tyr48Phe) 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: 33)
• Consequence: REEP5 ENST00000379638.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.88

Genes affected

REEP5 (HGNC:30077): (receptor accessory protein 5) Predicted to be involved in endoplasmic reticulum organization and regulation of intracellular transport. Located in endoplasmic reticulum tubular network. [provided by Alliance of Genome Resources, Apr 2022]

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
REEP5	NM_005669.5	c.143A>T	p.Tyr48Phe	missense_variant	2/5	ENST00000379638.9	NP_005660.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP5	ENST00000379638.9	c.143A>T	p.Tyr48Phe	missense_variant	2/5	1	NM_005669.5	ENSP00000368959	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

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

Mar 31, 2024

The c.143A>T (p.Y48F) alteration is located in exon 2 (coding exon 2) of the REEP5 gene. This alteration results from a A to T substitution at nucleotide position 143, causing the tyrosine (Y) at amino acid position 48 to be replaced by a phenylalanine (F). 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	0.30
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.;T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Pathogenic	3.0	M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.028	D;D;D;D
Sift4G	Uncertain	0.023	D;T;.;T
Polyphen		0.23	B;P;.;.
Vest4		0.67
MutPred		0.58		Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);.;Loss of helix (P = 0.3949);
MVP		0.47
MPC		0.22
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.72
gMVP		0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs1396979037; hg19: chr5-112256929;