chr5-177306544-C-A

Variant names:

• chr5-177306544-C-A
• rs778485653
• NM_013237.4:c.634C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_013237.4(PRELID1):​c.634C>A​(p.Gln212Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,609,792 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000028 (2 hom.)
• Consequence: PRELID1 NM_013237.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022721857).
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

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.634C>A	p.Gln212Lys	missense	Exon 5 of 5	NP_037369.1	Q9Y255-1
	PRELID1	NM_001271828.2		c.601C>A	p.Gln201Lys	missense	Exon 5 of 5	NP_001258757.1	Q9Y255-2
	MXD3	NM_001142935.2		c.*575G>T		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.634C>A	p.Gln212Lys	missense	Exon 5 of 5	ENSP00000302114.4	Q9Y255-1
	PRELID1	ENST00000503216.5	TSL:1	c.601C>A	p.Gln201Lys	missense	Exon 5 of 5	ENSP00000427097.1	Q9Y255-2
	PRELID1	ENST00000902811.1		c.646C>A	p.Gln216Lys	missense	Exon 5 of 5	ENSP00000572870.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000798 AC: 19 AN: 238220 AF XY: 0.0000925

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: 0.0000281 AC: 41 AN: 1457624 Hom.: 2 Cov.: 35 AF XY: 0.0000386 AC XY: 28 AN XY: 724782

African (AFR) AF: 0.00 AC: 0 AN: 33338

American (AMR) AF: 0.00 AC: 0 AN: 44326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.000421 AC: 36 AN: 85424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110354

Other (OTH) AF: 0.0000831 AC: 5 AN: 60194

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000909 AC: 11

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	0.073
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.49	N
PhyloP100		2.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.078
Sift	Benign	0.73	T
Sift4G	Benign	0.88	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.28		Gain of methylation at Q212 (P = 0.0114)
MVP		0.12
MPC		0.78
ClinPred		0.057	T
GERP RS		4.4
Varity_R		0.14
gMVP		0.22
Mutation Taster		=88/12	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: rs778485653; hg19: chr5-176733545;