Genetic Variant MID1IP1:p.Leu43Leu (chrX-38805075-G-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021242.6(MID1IP1):c.129G>C(p.Leu43Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,210,252 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000040 ( 0 hom. 16 hem. )

Consequence

MID1IP1
NM_021242.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.09

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 Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant X-38805075-G-C is Benign according to our data. Variant chrX-38805075-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2660302.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.09 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID1IP1	NM_021242.6 link	c.129G>C	p.Leu43Leu	synonymous_variant	Exon 3 of 3	ENST00000614558.3	NP_067065.1	Q9NPA3
MID1IP1	NM_001098790.2 link	c.129G>C	p.Leu43Leu	synonymous_variant	Exon 3 of 3		NP_001092260.1	Q9NPA3
MID1IP1	NM_001098791.2 link	c.129G>C	p.Leu43Leu	synonymous_variant	Exon 2 of 2		NP_001092261.1	Q9NPA3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MID1IP1	ENST00000614558.3 link	c.129G>C	p.Leu43Leu	synonymous_variant	Exon 3 of 3	5	NM_021242.6	ENSP00000483547.1	Q9NPA3
MID1IP1	ENST00000336949.7 link	c.129G>C	p.Leu43Leu	synonymous_variant	Exon 2 of 2	1		ENSP00000338706.6	Q9NPA3
MID1IP1	ENST00000378474.3 link	c.129G>C	p.Leu43Leu	synonymous_variant	Exon 3 of 3	1		ENSP00000367735.3	Q9NPA3
MID1IP1	ENST00000457894.5 link	c.129G>C	p.Leu43Leu	synonymous_variant	Exon 2 of 2	3		ENSP00000416670.1	Q9NPA3

Frequencies

GnomAD3 genomes

AF:

0.0000355

AC:

AN:

112567

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34721

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000563

Gnomad OTH

AF:

0.000663

GnomAD3 exomes

AF:

0.0000385

AC:

AN:

182020

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

66634

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000863

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000401

AC:

AN:

1097685

Hom.:

Cov.:

AF XY:

0.0000441

AC XY:

AN XY:

363097

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000487

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000355

AC:

AN:

112567

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34721

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000563

Gnomad4 OTH

AF:

0.000663

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MID1IP1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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