rs749949801

Variant names:

• chr14-36314598-C-G
• rs749949801
• NM_016586.3:c.485G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-36314598-C-G
• chr14-36314598-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016586.3(MBIP):​c.485G>C​(p.Arg162Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. R162Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MBIP NM_016586.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.34
• Publications: 0 publications found

Genes affected

MBIP (HGNC:20427): (MAP3K12 binding inhibitory protein 1) Enables identical protein binding activity and protein kinase inhibitor activity. Involved in histone H3 acetylation; positive regulation of JNK cascade; and positive regulation of gene expression. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016586.3. 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
	MBIP	NM_016586.3	MANE Select	c.485G>C	p.Arg162Pro	missense	Exon 4 of 9	NP_057670.2	Q9NS73-1
	MBIP	NM_001144891.2		c.485G>C	p.Arg162Pro	missense	Exon 4 of 9	NP_001138363.1	Q9NS73-5
	MBIP	NM_001308110.2		c.485G>C	p.Arg162Pro	missense	Exon 4 of 8	NP_001295039.1	Q9NS73-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBIP	ENST00000416007.9	TSL:1 MANE Select	c.485G>C	p.Arg162Pro	missense	Exon 4 of 9	ENSP00000399718.2	Q9NS73-1
	MBIP	ENST00000318473.11	TSL:1	c.485G>C	p.Arg162Pro	missense	Exon 4 of 9	ENSP00000324444.5	Q9NS73-5
	MBIP	ENST00000359527.11	TSL:1	c.485G>C	p.Arg162Pro	missense	Exon 4 of 8	ENSP00000352517.5	Q9NS73-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-6.8	D
REVEL	Pathogenic	0.86
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.98
MutPred		0.75		Loss of helix (P = 0.0068)
MVP		0.96
MPC		0.54
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.96
gMVP		0.89
Mutation Taster		=69/31	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: rs749949801; hg19: chr14-36783804;