5-145823122-T-A

Position:

• chr5-145823122-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_205846.3(PRELID2):​c.88A>T​(p.Met30Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRELID2 NM_205846.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

Genes affected

PRELID2 (HGNC:28306): (PRELI domain containing 2) Predicted to enable phosphatidic acid transfer activity. Predicted to be involved in phospholipid transport. Predicted to be active in mitochondrial intermembrane space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18293193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRELID2	NM_205846.3	c.88A>T	p.Met30Leu	missense_variant	2/7	ENST00000683046.1	NP_995318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRELID2	ENST00000683046.1	c.88A>T	p.Met30Leu	missense_variant	2/7		NM_205846.3	ENSP00000506938.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 23

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 21, 2023

The c.88A>T (p.M30L) alteration is located in exon 2 (coding exon 2) of the PRELID2 gene. This alteration results from a A to T substitution at nucleotide position 88, causing the methionine (M) at amino acid position 30 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.019	T;.;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.69	T;D;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;L;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.24
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.0010	B;.;.;B
Vest4		0.38
MutPred		0.49		Loss of solvent accessibility (P = 0.0595);.;Loss of solvent accessibility (P = 0.0595);Loss of solvent accessibility (P = 0.0595);
MVP		0.030
MPC		0.070
ClinPred		0.73	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-145202685;