5-177304794-C-T

Variant names:

• chr5-177304794-C-T
• NM_013237.4:c.262C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_013237.4(PRELID1):​c.262C>T​(p.Pro88Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRELID1 NM_013237.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.70

Genes affected

PRELID1 (HGNC:30255): (PRELI domain containing 1) This gene encodes a member of the late embryogenesis abundant motif-containing protein family. The encoded protein is localized to mitochondria and may function as a cytoprotectant by regulating cell death and differentiation. Alternative splicing results in multiple transcript variants encoding different isoforms. Several related pseudogenes have been identified. [provided by RefSeq, Nov 2012]

MXD3 (HGNC:14008): (MAX dimerization protein 3) This gene encodes a member of the Myc superfamily of basic helix-loop-helix leucine zipper transcriptional regulators. The encoded protein forms a heterodimer with the cofactor MAX which binds specific E-box DNA motifs in the promoters of target genes and regulates their transcription. Disruption of the MAX-MXD3 complex is associated with uncontrolled cell proliferation and tumorigenesis. Transcript variants of this gene encoding different isoforms have been described.[provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRELID1	NM_013237.4	c.262C>T	p.Pro88Ser	missense_variant	Exon 2 of 5	ENST00000303204.9	NP_037369.1
PRELID1	NM_001271828.2	c.262C>T	p.Pro88Ser	missense_variant	Exon 2 of 5		NP_001258757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRELID1	ENST00000303204.9	c.262C>T	p.Pro88Ser	missense_variant	Exon 2 of 5	1	NM_013237.4	ENSP00000302114.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.262C>T (p.P88S) alteration is located in exon 2 (coding exon 2) of the PRELID1 gene. This alteration results from a C to T substitution at nucleotide position 262, causing the proline (P) at amino acid position 88 to be replaced by a serine (S). 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	Uncertain	0.52
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.8	D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.030	D;D
Polyphen		0.90	P;.
Vest4		0.82
MutPred		0.67		Gain of disorder (P = 0.0836);Gain of disorder (P = 0.0836);
MVP		0.26
MPC		1.6
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.91
gMVP		0.76

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: chr5-176731795;