5-179840949-T-C

Variant names:

• chr5-179840949-T-C
• rs248248
• NM_016175.4:c.460A>G

Variant summary

Our verdict is Benign. Variant got -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. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRNIP	NM_016175.4	c.460A>G	p.Arg154Gly	missense_variant	Exon 6 of 7	ENST00000292586.11	NP_057259.2
MRNIP	NM_001017987.3	c.295A>G	p.Arg99Gly	missense_variant	Exon 4 of 5		NP_001017987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRNIP	ENST00000292586.11	c.460A>G	p.Arg154Gly	missense_variant	Exon 6 of 7	1	NM_016175.4	ENSP00000292586.6

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

GnomAD3 exomes AF: 0.772 AC: 181956 AN: 235568 Hom.: 70914 AF XY: 0.763 AC XY: 97538 AN XY: 127796

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 SAS exome AF: 0.766

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

Gnomad4 AFR exome AF: 0.928

Gnomad4 AMR exome AF: 0.869

Gnomad4 ASJ exome AF: 0.743

Gnomad4 EAS exome AF: 0.919

Gnomad4 SAS exome AF: 0.765

Gnomad4 FIN exome AF: 0.756

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.742

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

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.906

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.779

Alfa AF: 0.718 Hom.: 89801

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 v4.3

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;T;.;T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.089	N
MetaRNN	Benign	7.8e-7	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.69	N;N;N;N;N;N
REVEL	Benign	0.037
Sift	Benign	0.29	T;T;T;T;T;T
Sift4G	Benign	0.27	T;T;D;T;D;T
Polyphen		0.0	B;B;.;.;.;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

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

Publications

LitVar

Other links and lift over

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