Genetic Variant MRNIP:c.*2614G>A (chr5-179838216-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000518219(MRNIP):c.*2614G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 360,462 control chromosomes in the GnomAD database, including 626 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 0.061 ( 318 hom., cov: 33)

Exomes 𝑓: 0.048 ( 308 hom. )

Consequence

MRNIP
ENST00000518219 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.164

Variant links:

Genes affected

MRNIP (HGNC:30817): (MRN complex interacting protein) Enables chromatin binding activity. Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; regulation of double-strand break repair; and response to ionizing radiation. Located in nucleoplasm. Colocalizes with Mre11 complex. [provided by Alliance of Genome Resources, Apr 2022]

MRNIP links:

SQSTM1 (HGNC:11280): (sequestosome 1) This gene encodes a multifunctional protein that binds ubiquitin and regulates activation of the nuclear factor kappa-B (NF-kB) signaling pathway. The protein functions as a scaffolding/adaptor protein in concert with TNF receptor-associated factor 6 to mediate activation of NF-kB in response to upstream signals. Alternatively spliced transcript variants encoding either the same or different isoforms have been identified for this gene. Mutations in this gene result in sporadic and familial Paget disease of bone. [provided by RefSeq, Mar 2009]

SQSTM1 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRNIP	NM_016175.4 link	c.538-331G>A		intron_variant	Intron 6 of 6	ENST00000292586.11	NP_057259.2
SQSTM1	NM_003900.5 link	c.*1623C>T		downstream_gene_variant		ENST00000389805.9	NP_003891.1	Q13501-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRNIP	ENST00000292586.11 link	c.538-331G>A		intron_variant	Intron 6 of 6	1	NM_016175.4	ENSP00000292586.6		Q6NTE8-1
SQSTM1	ENST00000389805.9 link	c.*1623C>T		downstream_gene_variant		1	NM_003900.5	ENSP00000374455.4		Q13501-1

Frequencies

GnomAD3 genomes

AF:

0.0614

AC:

9348

AN:

152138

Hom.:

318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0843

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.0626

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0284

Gnomad FIN

AF:

0.0465

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0524

Gnomad OTH

AF:

0.0644

GnomAD4 exome

AF:

0.0477

AC:

9936

AN:

208206

Hom.:

308

Cov.:

AF XY:

0.0461

AC XY:

5005

AN XY:

108596

show subpopulations

Gnomad4 AFR exome

AF:

0.0852

Gnomad4 AMR exome

AF:

0.0434

Gnomad4 ASJ exome

AF:

0.0928

Gnomad4 EAS exome

AF:

0.0000807

Gnomad4 SAS exome

AF:

0.0239

Gnomad4 FIN exome

AF:

0.0402

Gnomad4 NFE exome

AF:

0.0524

Gnomad4 OTH exome

AF:

0.0546

GnomAD4 genome

AF:

0.0614

AC:

9349

AN:

152256

Hom.:

318

Cov.:

AF XY:

0.0599

AC XY:

4459

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0842

Gnomad4 AMR

AF:

0.0626

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0282

Gnomad4 FIN

AF:

0.0465

Gnomad4 NFE

AF:

0.0524

Gnomad4 OTH

AF:

0.0627

Alfa

AF:

0.0555

Hom.:

172

Bravo

AF:

0.0630

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.8

DANN

Benign

0.64

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