5-145817979-T-G

Position:

• chr5-145817979-T-G

Variant summary

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

The NM_205846.3(PRELID2):​c.283A>C​(p.Ile95Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,570 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PRELID2 NM_205846.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28

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=0.10898143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRELID2	NM_205846.3	c.283A>C	p.Ile95Leu	missense_variant	4/7	ENST00000683046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRELID2	ENST00000683046.1	c.283A>C	p.Ile95Leu	missense_variant	4/7		NM_205846.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459570 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726042

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

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

May 18, 2022

The c.319A>C (p.I107L) alteration is located in exon 5 (coding exon 5) of the PRELID2 gene. This alteration results from a A to C substitution at nucleotide position 319, causing the isoleucine (I) at amino acid position 107 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	0.18
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Benign	0.67
DEOGEN2	Benign	0.0037	T;.;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.;.;.
MutationTaster	Benign	0.65	D;D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.56	N;N;N;N
REVEL	Benign	0.080
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0010	B;.;.;B
Vest4		0.30
MutPred		0.63		Loss of MoRF binding (P = 0.1092);.;.;.;
MVP		0.014
MPC		0.073
ClinPred		0.37	T
GERP RS		5.8
Varity_R		0.11
gMVP		0.35

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: rs200308330; hg19: chr5-145197542;