rs248248

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-179840949-T-A
• chr5-179840949-T-C
• chr5-179840949-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016175.4(MRNIP):​c.460A>T​(p.Arg154Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08266145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRNIP	NM_016175.4	c.460A>T	p.Arg154Trp	missense_variant	Exon 6 of 7	ENST00000292586.11	NP_057259.2
MRNIP	NM_001017987.3	c.295A>T	p.Arg99Trp	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>T	p.Arg154Trp	missense_variant	Exon 6 of 7	1	NM_016175.4	ENSP00000292586.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1452718 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 721950

African (AFR) AF: 0.00 AC: 0 AN: 33336

American (AMR) AF: 0.00 AC: 0 AN: 44098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.00 AC: 0 AN: 84780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107752

Other (OTH) AF: 0.00 AC: 0 AN: 59934

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T;T;.;T;T;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.083	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.61
PROVEAN	Benign	-1.8	N;N;N;N;D;N
REVEL	Benign	0.10
Sift	Uncertain	0.014	D;D;D;D;D;D
Sift4G	Uncertain	0.021	D;D;D;D;D;D
Polyphen		0.94	P;P;.;.;.;P
Vest4		0.15
MutPred		0.19		Loss of phosphorylation at T156 (P = 0.0514);.;.;Loss of phosphorylation at T156 (P = 0.0514);.;Loss of phosphorylation at T156 (P = 0.0514);
MVP		0.21
MPC		0.25
ClinPred		0.42	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.074
gMVP		0.088
Mutation Taster		=99/1	polymorphism

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;