rs1650893

chr5-179853379-T-Achr5-179853379-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016175.4(MRNIP):c.125A>T(p.Gln42Leu) variant causes a missense, splice region 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. 13/21 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q42R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRNIP NM_016175.4 missense, splice_region
• Scores: Splicing: ADA: 0.3149
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09690961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRNIP	NM_016175.4	c.125A>T	p.Gln42Leu	missense_variant, splice_region_variant	2/7	ENST00000292586.11
MRNIP	NM_001017987.3	c.125A>T	p.Gln42Leu	missense_variant, splice_region_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRNIP	ENST00000292586.11	c.125A>T	p.Gln42Leu	missense_variant, splice_region_variant	2/7	1	NM_016175.4	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	19
Dann	Uncertain	0.98
DEOGEN2	Benign	0.050	T;T;.;T;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.097	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PROVEAN	Uncertain	-3.4	D;D;D;D;D;D
REVEL	Benign	0.025
Sift	Uncertain	0.015	D;D;D;D;D;D
Sift4G	Uncertain	0.046	D;D;D;D;D;D
Polyphen		0.11	B;B;.;.;B;.
Vest4		0.34
MutPred		0.42		Loss of disorder (P = 0.036);Loss of disorder (P = 0.036);Loss of disorder (P = 0.036);Loss of disorder (P = 0.036);Loss of disorder (P = 0.036);Loss of disorder (P = 0.036);
MVP		0.20
MPC		0.079
ClinPred		0.42	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.31
dbscSNV1_RF	Benign	0.46
SpliceAI score (max)		0.15		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: rs1650893; hg19: chr5-179280379;