NM_013237.4:c.651G>T

Variant names:

• chr5-177306561-G-T
• rs775089583
• NM_013237.4:c.651G>T

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.651G>T​(p.Gln217His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,457,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: PRELID1 NM_013237.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.229
• 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=0.09765822).

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.651G>T	p.Gln217His	missense	Exon 5 of 5	NP_037369.1	Q9Y255-1
	PRELID1	NM_001271828.2		c.618G>T	p.Gln206His	missense	Exon 5 of 5	NP_001258757.1	Q9Y255-2
	MXD3	NM_001142935.2		c.*558C>A		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.651G>T	p.Gln217His	missense	Exon 5 of 5	ENSP00000302114.4	Q9Y255-1
	PRELID1	ENST00000503216.5	TSL:1	c.618G>T	p.Gln206His	missense	Exon 5 of 5	ENSP00000427097.1	Q9Y255-2
	PRELID1	ENST00000902811.1		c.663G>T	p.Gln221His	missense	Exon 5 of 5	ENSP00000572870.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000126 AC: 3 AN: 237990 AF XY: 0.00000772

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1457404 Hom.: 0 Cov.: 35 AF XY: 0.0000124 AC XY: 9 AN XY: 724608

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.00 AC: 0 AN: 44276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.000141 AC: 12 AN: 85384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110328

Other (OTH) AF: 0.0000498 AC: 3 AN: 60182

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000827 AC: 1

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	0.089
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.23
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.099
Sift	Benign	0.11	T
Sift4G	Benign	0.16	T
Polyphen		0.84	P
Vest4		0.23
MutPred		0.18		Loss of helix (P = 0.028)
MVP		0.16
MPC		0.58
ClinPred		0.080	T
GERP RS		0.19
Varity_R		0.053
gMVP		0.37
Mutation Taster		=82/18	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: rs775089583; hg19: chr5-176733562;