14-36320557-C-T

Variant names:

• chr14-36320557-C-T
• rs1880845422
• NM_016586.3:c.32G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_016586.3(MBIP):​c.32G>A​(p.Ser11Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MBIP NM_016586.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.704

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]

ENSG00000283098 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052559525).
• BP6: Variant 14-36320557-C-T is Benign according to our data. Variant chr14-36320557-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3124070.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBIP	NM_016586.3	c.32G>A	p.Ser11Asn	missense_variant	Exon 1 of 9	ENST00000416007.9	NP_057670.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBIP	ENST00000416007.9	c.32G>A	p.Ser11Asn	missense_variant	Exon 1 of 9	1	NM_016586.3	ENSP00000399718.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461160 Hom.: 0 Cov.: 59 AF XY: 0.00000138 AC XY: 1 AN XY: 726888

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 20, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.34
DANN	Benign	0.83
DEOGEN2	Benign	0.013	T;T;.;.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.55	T;T;T;T;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.053	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N;.;N;N;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.68	N;.;N;N;.;.
REVEL	Benign	0.034
Sift	Benign	0.26	T;.;T;T;.;.
Sift4G	Benign	0.13	T;T;T;T;.;D
Polyphen		0.0	B;.;B;B;.;.
Vest4		0.084
MutPred		0.11		Loss of phosphorylation at S11 (P = 0.037);Loss of phosphorylation at S11 (P = 0.037);Loss of phosphorylation at S11 (P = 0.037);Loss of phosphorylation at S11 (P = 0.037);Loss of phosphorylation at S11 (P = 0.037);Loss of phosphorylation at S11 (P = 0.037);
MVP		0.42
MPC		0.075
ClinPred		0.12	T
GERP RS		-4.2
Varity_R		0.072
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs1880845422; hg19: chr14-36789763;