chr5-179840949-T-C

Variant names:

• chr5-179840949-T-C
• rs248248
• NM_016175.4:c.460A>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.460A>G​(p.Arg154Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 1,603,424 control chromosomes in the GnomAD database, including 430,849 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (48216 hom., cov: 30)
  • Exomes 𝑓: 0.72 (382633 hom.)
• Consequence: MRNIP NM_016175.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607
• Publications: 40 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=7.785444E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016175.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRNIP	NM_016175.4	MANE Select	c.460A>G	p.Arg154Gly	missense	Exon 6 of 7	NP_057259.2
	MRNIP	NM_001017987.3		c.295A>G	p.Arg99Gly	missense	Exon 4 of 5	NP_001017987.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRNIP	ENST00000292586.11	TSL:1 MANE Select	c.460A>G	p.Arg154Gly	missense	Exon 6 of 7	ENSP00000292586.6
	MRNIP	ENST00000523084.5	TSL:1	c.58A>G	p.Arg20Gly	missense	Exon 5 of 6	ENSP00000429107.1
	MRNIP	ENST00000518219.5	TSL:1	c.460A>G	p.Arg154Gly	missense	Exon 6 of 6	ENSP00000428460.1

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120092 AN: 151872 Hom.: 48163 Cov.: 30

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.777

GnomAD2 exomes AF: 0.772 AC: 181956 AN: 235568 AF XY: 0.763

Gnomad AFR exome AF: 0.921

Gnomad AMR exome AF: 0.875

Gnomad ASJ exome AF: 0.749

Gnomad EAS exome AF: 0.911

Gnomad FIN exome AF: 0.760

Gnomad NFE exome AF: 0.703

Gnomad OTH exome AF: 0.751

GnomAD4 exome AF: 0.724 AC: 1050118 AN: 1451436 Hom.: 382633 Cov.: 39 AF XY: 0.724 AC XY: 522476 AN XY: 721366

African (AFR) AF: 0.928 AC: 30935 AN: 33330

American (AMR) AF: 0.869 AC: 38285 AN: 44078

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 19227 AN: 25886

East Asian (EAS) AF: 0.919 AC: 36243 AN: 39452

South Asian (SAS) AF: 0.765 AC: 64851 AN: 84742

European-Finnish (FIN) AF: 0.756 AC: 39446 AN: 52198

Middle Eastern (MID) AF: 0.762 AC: 3993 AN: 5240

European-Non Finnish (NFE) AF: 0.698 AC: 772724 AN: 1106622

Other (OTH) AF: 0.742 AC: 44414 AN: 59888

GnomAD4 genome AF: 0.791 AC: 120204 AN: 151988 Hom.: 48216 Cov.: 30 AF XY: 0.795 AC XY: 59050 AN XY: 74274

African (AFR) AF: 0.917 AC: 38022 AN: 41476

American (AMR) AF: 0.829 AC: 12665 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2611 AN: 3466

East Asian (EAS) AF: 0.906 AC: 4645 AN: 5128

South Asian (SAS) AF: 0.780 AC: 3757 AN: 4814

European-Finnish (FIN) AF: 0.753 AC: 7959 AN: 10568

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48008 AN: 67936

Other (OTH) AF: 0.779 AC: 1647 AN: 2114

Alfa AF: 0.729 Hom.: 171943

Bravo AF: 0.801

TwinsUK AF: 0.694 AC: 2575

ALSPAC AF: 0.689 AC: 2656

ESP6500AA AF: 0.909 AC: 4006

ESP6500EA AF: 0.706 AC: 6075

ExAC AF: 0.758 AC: 91617

Asia WGS AF: 0.858 AC: 2984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	19
DANN	Benign	0.87
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.089	N
MetaRNN	Benign	7.8e-7	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.61
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.037
Sift	Benign	0.29	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.024
MPC		0.084
ClinPred		0.0043	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.051
gMVP		0.069
Mutation Taster		=100/0	polymorphism (auto)

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: rs248248; hg19: chr5-179267949; COSMIC: COSV52971827; COSMIC: COSV52971827;