5-179853379-T-C

Variant names:

• chr5-179853379-T-C
• rs1650893
• NM_016175.4:c.125A>G

Variant summary

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

The NM_016175.4(MRNIP):​c.125A>G​(p.Gln42Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,611,300 control chromosomes in the GnomAD database, including 279,228 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (35991 hom., cov: 33)
  • Exomes 𝑓: 0.57 (243237 hom.)
• Consequence: MRNIP NM_016175.4 missense, splice_region
• Scores: Splicing: ADA: 0.06061
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 58 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.3017577E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRNIP	NM_016175.4	c.125A>G	p.Gln42Arg	missense_variant, splice_region_variant	Exon 2 of 7	ENST00000292586.11	NP_057259.2
MRNIP	NM_001017987.3	c.125A>G	p.Gln42Arg	missense_variant, splice_region_variant	Exon 2 of 5		NP_001017987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRNIP	ENST00000292586.11	c.125A>G	p.Gln42Arg	missense_variant, splice_region_variant	Exon 2 of 7	1	NM_016175.4	ENSP00000292586.6

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102322 AN: 152062 Hom.: 35935 Cov.: 33

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.639

GnomAD2 exomes AF: 0.640 AC: 160549 AN: 250738 AF XY: 0.626

Gnomad AFR exome AF: 0.882

Gnomad AMR exome AF: 0.804

Gnomad ASJ exome AF: 0.632

Gnomad EAS exome AF: 0.797

Gnomad FIN exome AF: 0.621

Gnomad NFE exome AF: 0.541

Gnomad OTH exome AF: 0.613

GnomAD4 exome AF: 0.571 AC: 832991 AN: 1459120 Hom.: 243237 Cov.: 34 AF XY: 0.571 AC XY: 414735 AN XY: 726086

African (AFR) AF: 0.891 AC: 29817 AN: 33452

American (AMR) AF: 0.792 AC: 35434 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 16266 AN: 26116

East Asian (EAS) AF: 0.790 AC: 31339 AN: 39692

South Asian (SAS) AF: 0.620 AC: 53446 AN: 86234

European-Finnish (FIN) AF: 0.617 AC: 32486 AN: 52640

Middle Eastern (MID) AF: 0.613 AC: 3530 AN: 5760

European-Non Finnish (NFE) AF: 0.536 AC: 594763 AN: 1110178

Other (OTH) AF: 0.595 AC: 35910 AN: 60334

GnomAD4 genome AF: 0.673 AC: 102435 AN: 152180 Hom.: 35991 Cov.: 33 AF XY: 0.678 AC XY: 50410 AN XY: 74402

African (AFR) AF: 0.877 AC: 36422 AN: 41548

American (AMR) AF: 0.722 AC: 11043 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2176 AN: 3470

East Asian (EAS) AF: 0.785 AC: 4053 AN: 5164

South Asian (SAS) AF: 0.631 AC: 3045 AN: 4826

European-Finnish (FIN) AF: 0.625 AC: 6617 AN: 10584

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36992 AN: 67978

Other (OTH) AF: 0.642 AC: 1355 AN: 2112

Alfa AF: 0.601 Hom.: 65549

Bravo AF: 0.689

TwinsUK AF: 0.522 AC: 1936

ALSPAC AF: 0.528 AC: 2035

ESP6500AA AF: 0.868 AC: 3826

ESP6500EA AF: 0.546 AC: 4692

ExAC AF: 0.636 AC: 77264

Asia WGS AF: 0.721 AC: 2510 AN: 3478

EpiCase AF: 0.541

EpiControl AF: 0.541

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.7
DANN	Benign	0.57
DEOGEN2	Benign	0.0064	T;T;.;T;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.017	N
MetaRNN	Benign	0.000014	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.018
PROVEAN	Benign	1.4	N;N;N;N;N;N
REVEL	Benign	0.019
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0	B;B;.;.;B;.
Vest4		0.024
MPC		0.071
ClinPred		0.000018	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.088
Mutation Taster		=75/25	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.061
dbscSNV1_RF	Benign	0.36
SpliceAI score (max)		0.13		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: rs1650893; hg19: chr5-179280379; COSMIC: COSV52971773;