NM_013237.4:c.512-82A>G

Variant names:

• chr5-177306340-A-G
• rs4073745
• NM_013237.4:c.512-82A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013237.4(PRELID1):​c.512-82A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,597,982 control chromosomes in the GnomAD database, including 87,720 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (15397 hom., cov: 29)
  • Exomes 𝑓: 0.30 (72323 hom.)
• Consequence: PRELID1 NM_013237.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

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.512-82A>G		intron	N/A	NP_037369.1	Q9Y255-1
	MXD3	NM_001142935.2		c.*779T>C		3_prime_UTR	Exon 6 of 6	NP_001136407.1	Q9BW11-3
	PRELID1	NM_001271828.2		c.512-115A>G		intron	N/A	NP_001258757.1	Q9Y255-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRELID1	ENST00000303204.9	TSL:1 MANE Select	c.512-82A>G		intron	N/A	ENSP00000302114.4	Q9Y255-1
	PRELID1	ENST00000503216.5	TSL:1	c.512-115A>G		intron	N/A	ENSP00000427097.1	Q9Y255-2
	MXD3	ENST00000427908.6	TSL:2	c.*779T>C		3_prime_UTR	Exon 6 of 6	ENSP00000416921.2	Q9BW11-3

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61239 AN: 151430 Hom.: 15369 Cov.: 29

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.0378

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.391

GnomAD2 exomes AF: 0.301 AC: 69962 AN: 232314 AF XY: 0.305

Gnomad AFR exome AF: 0.723

Gnomad AMR exome AF: 0.171

Gnomad ASJ exome AF: 0.416

Gnomad EAS exome AF: 0.0369

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.318

GnomAD4 exome AF: 0.303 AC: 438816 AN: 1446434 Hom.: 72323 Cov.: 31 AF XY: 0.304 AC XY: 218547 AN XY: 719006

African (AFR) AF: 0.724 AC: 24000 AN: 33172

American (AMR) AF: 0.186 AC: 7969 AN: 42896

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 10849 AN: 25860

East Asian (EAS) AF: 0.0325 AC: 1282 AN: 39440

South Asian (SAS) AF: 0.342 AC: 29077 AN: 85048

European-Finnish (FIN) AF: 0.288 AC: 15220 AN: 52856

Middle Eastern (MID) AF: 0.431 AC: 2469 AN: 5732

European-Non Finnish (NFE) AF: 0.298 AC: 328494 AN: 1101612

Other (OTH) AF: 0.325 AC: 19456 AN: 59818

GnomAD4 genome AF: 0.405 AC: 61316 AN: 151548 Hom.: 15397 Cov.: 29 AF XY: 0.395 AC XY: 29263 AN XY: 74042

African (AFR) AF: 0.707 AC: 29142 AN: 41236

American (AMR) AF: 0.274 AC: 4175 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1420 AN: 3470

East Asian (EAS) AF: 0.0381 AC: 196 AN: 5146

South Asian (SAS) AF: 0.313 AC: 1502 AN: 4798

European-Finnish (FIN) AF: 0.292 AC: 3067 AN: 10486

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.304 AC: 20636 AN: 67874

Other (OTH) AF: 0.390 AC: 818 AN: 2100

Alfa AF: 0.392 Hom.: 2784

Bravo AF: 0.417

Asia WGS AF: 0.237 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.58
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4073745; hg19: chr5-176733341; COSMIC: COSV57463001; COSMIC: COSV57463001;