dbSNP rs4073745: PRELID1:c.512-82A>G (chr5-177306340-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001142935.2(MXD3):c.*779T>C variant causes a 3 prime UTR 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

MXD3
NM_001142935.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.371

Variant links:

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]

PRELID1 links:

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]

MXD3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRELID1	NM_013237.4 link	c.512-82A>G	intron_variant	Intron 4 of 4	ENST00000303204.9	NP_037369.1	Q9Y255-1
MXD3	NM_001142935.2 link	c.*779T>C	3_prime_UTR_variant	Exon 6 of 6		NP_001136407.1	Q9BW11-3
PRELID1	NM_001271828.2 link	c.512-115A>G	intron_variant	Intron 4 of 4		NP_001258757.1	Q9Y255-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRELID1	ENST00000303204.9 link	c.512-82A>G		intron_variant	Intron 4 of 4	1	NM_013237.4	ENSP00000302114.4		Q9Y255-1

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61239

AN:

151430

Hom.:

15369

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.301

AC:

69962

AN:

232314

Hom.:

12745

AF XY:

0.305

AC XY:

38468

AN XY:

126230

show subpopulations

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 SAS exome

AF:

0.344

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.:

AF XY:

0.304

AC XY:

218547

AN XY:

719006

show subpopulations

Gnomad4 AFR exome

AF:

0.724

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.420

Gnomad4 EAS exome

AF:

0.0325

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.288

Gnomad4 NFE exome

AF:

0.298

Gnomad4 OTH exome

AF:

0.325

GnomAD4 genome

AF:

0.405

AC:

61316

AN:

151548

Hom.:

15397

Cov.:

AF XY:

0.395

AC XY:

29263

AN XY:

74042

show subpopulations

Gnomad4 AFR

AF:

0.707

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.409

Gnomad4 EAS

AF:

0.0381

Gnomad4 SAS

AF:

0.313

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.304

Gnomad4 OTH

AF:

0.390

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.3

DANN

Benign

0.58

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over