5-177306527-A-G

Variant names:

• chr5-177306527-A-G
• rs756632017
• NM_013237.4:c.617A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013237.4(PRELID1):​c.617A>G​(p.Lys206Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,612,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: PRELID1 NM_013237.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1148594).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013237.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRELID1	NM_013237.4	MANE Select	c.617A>G	p.Lys206Arg	missense	Exon 5 of 5	NP_037369.1	Q9Y255-1
	PRELID1	NM_001271828.2		c.584A>G	p.Lys195Arg	missense	Exon 5 of 5	NP_001258757.1	Q9Y255-2
	MXD3	NM_001142935.2		c.*592T>C		3_prime_UTR	Exon 6 of 6	NP_001136407.1	Q9BW11-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRELID1	ENST00000303204.9	TSL:1 MANE Select	c.617A>G	p.Lys206Arg	missense	Exon 5 of 5	ENSP00000302114.4	Q9Y255-1
	PRELID1	ENST00000503216.5	TSL:1	c.584A>G	p.Lys195Arg	missense	Exon 5 of 5	ENSP00000427097.1	Q9Y255-2
	PRELID1	ENST00000902811.1		c.629A>G	p.Lys210Arg	missense	Exon 5 of 5	ENSP00000572870.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152004 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000864 AC: 21 AN: 243086 AF XY: 0.0000832

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000472

Gnomad NFE exome AF: 0.000164

Gnomad OTH exome AF: 0.000337

GnomAD4 exome AF: 0.0000733 AC: 107 AN: 1460372 Hom.: 0 Cov.: 35 AF XY: 0.0000620 AC XY: 45 AN XY: 726362

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 85924

European-Finnish (FIN) AF: 0.0000564 AC: 3 AN: 53194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000873 AC: 97 AN: 1111404

Other (OTH) AF: 0.0000994 AC: 6 AN: 60334

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152004 Hom.: 0 Cov.: 31 AF XY: 0.0000539 AC XY: 4 AN XY: 74224

African (AFR) AF: 0.0000242 AC: 1 AN: 41370

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000989 AC: 12

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T
Eigen	Benign	0.097
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.030
Sift	Benign	0.17	T
Sift4G	Benign	0.20	T
Polyphen		0.73	P
Vest4		0.12
MutPred		0.23		Gain of ubiquitination at K201 (P = 0.0325)
MVP		0.21
MPC		0.86
ClinPred		0.15	T
GERP RS		4.4
Varity_R		0.12
gMVP		0.093
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs756632017; hg19: chr5-176733528;