chr5-179853379-T-A

Variant names:

• chr5-179853379-T-A
• rs1650893
• ENST00000523084.5:c.-189A>T

Variant summary

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

The ENST00000523084.5(MRNIP):​c.-189A>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRNIP ENST00000523084.5 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.3149
• 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: 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=0.09690961).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000523084.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRNIP	NM_016175.4	MANE Select	c.125A>T	p.Gln42Leu	missense splice_region	Exon 2 of 7	NP_057259.2	Q6NTE8-1
	MRNIP	NM_001017987.3		c.125A>T	p.Gln42Leu	missense splice_region	Exon 2 of 5	NP_001017987.1	Q6NTE8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRNIP	ENST00000523084.5	TSL:1	c.-189A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000429107.1	E5RJC6
	MRNIP	ENST00000292586.11	TSL:1 MANE Select	c.125A>T	p.Gln42Leu	missense splice_region	Exon 2 of 7	ENSP00000292586.6	Q6NTE8-1
	MRNIP	ENST00000523084.5	TSL:1	c.-189A>T		splice_region	Exon 2 of 6	ENSP00000429107.1	E5RJC6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.1	T
PhyloP100		-0.018
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.025
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.046	D
Polyphen		0.11	B
Vest4		0.34
MutPred		0.42		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
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs1650893; hg19: chr5-179280379;