Variant X-38805142-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021242.6(MID1IP1):c.196C>T(p.Arg66Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,095,586 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. 5 hem. )

Consequence

MID1IP1
NM_021242.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00900

Variant links:

Genes affected

MID1IP1 (HGNC:20715): (MID1 interacting protein 1) Predicted to enable identical protein binding activity and protein C-terminus binding activity. Predicted to be involved in several processes, including negative regulation of microtubule depolymerization; positive regulation of fatty acid biosynthetic process; and protein polymerization. Predicted to be located in cytoplasm and microtubule cytoskeleton. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

MID1IP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22319528).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MID1IP1	NM_021242.6 linkuse as main transcript	c.196C>T	p.Arg66Cys	missense_variant	3/3	ENST00000614558.3	NP_067065.1
MID1IP1	NM_001098790.2 linkuse as main transcript	c.196C>T	p.Arg66Cys	missense_variant	3/3		NP_001092260.1
MID1IP1	NM_001098791.2 linkuse as main transcript	c.196C>T	p.Arg66Cys	missense_variant	2/2		NP_001092261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MID1IP1	ENST00000614558.3 linkuse as main transcript	c.196C>T	p.Arg66Cys	missense_variant	3/3	5	NM_021242.6	ENSP00000483547	P1
MID1IP1	ENST00000336949.7 linkuse as main transcript	c.196C>T	p.Arg66Cys	missense_variant	2/2	1		ENSP00000338706	P1
MID1IP1	ENST00000378474.3 linkuse as main transcript	c.196C>T	p.Arg66Cys	missense_variant	3/3	1		ENSP00000367735	P1
MID1IP1	ENST00000457894.5 linkuse as main transcript	c.196C>T	p.Arg66Cys	missense_variant	2/2	3		ENSP00000416670	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000227

AC:

AN:

176095

Hom.:

AF XY:

0.0000320

AC XY:

AN XY:

62505

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000386

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1095586

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

361352

show subpopulations

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:

0.0000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000202

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.196C>T (p.R66C) alteration is located in exon 2 (coding exon 1) of the MID1IP1 gene. This alteration results from a C to T substitution at nucleotide position 196, causing the arginine (R) at amino acid position 66 to be replaced by a cysteine (C). 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

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

T;T;T;T

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.65

.;T;.;.

M_CAP

Benign

0.029

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

L;L;L;L

MutationTaster

Benign

0.82

N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.1

.;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.026

.;D;D;D

Sift4G

Uncertain

0.046

D;D;D;D

Polyphen

0.91

P;P;P;P

Vest4

0.32

MutPred

0.63

Loss of solvent accessibility (P = 0.0561);Loss of solvent accessibility (P = 0.0561);Loss of solvent accessibility (P = 0.0561);Loss of solvent accessibility (P = 0.0561);

MVP

0.41

MPC

0.60

ClinPred

0.27

GERP RS

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.18

gMVP

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over