14-36300786-T-A

Variant names:

• chr14-36300786-T-A
• rs1228187948
• NM_016586.3:c.926A>T

Variant summary

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

The NM_016586.3(MBIP):​c.926A>T​(p.Gln309Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000428 in 1,403,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: MBIP NM_016586.3 missense, splice_region
• Scores: Splicing: ADA: 0.9996
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBIP	NM_016586.3	c.926A>T	p.Gln309Leu	missense_variant, splice_region_variant	Exon 8 of 9	ENST00000416007.9	NP_057670.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBIP	ENST00000416007.9	c.926A>T	p.Gln309Leu	missense_variant, splice_region_variant	Exon 8 of 9	1	NM_016586.3	ENSP00000399718.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000428 AC: 6 AN: 1403292 Hom.: 0 Cov.: 25 AF XY: 0.00000286 AC XY: 2 AN XY: 699146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.29e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.926A>T (p.Q309L) alteration is located in exon 8 (coding exon 8) of the MBIP gene. This alteration results from a A to T substitution at nucleotide position 926, causing the glutamine (Q) at amino acid position 309 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N;D
REVEL	Benign	0.088
Sift	Benign	0.11	T;D
Sift4G	Benign	0.21	T;D
Polyphen		0.74	P;P
Vest4		0.40
MutPred		0.16		Loss of disorder (P = 0.0699);Loss of disorder (P = 0.0699);
MVP		0.44
MPC		0.21
ClinPred		0.89	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.96
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: rs1228187948; hg19: chr14-36769992;