Variant X-38805467-A-G 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.521A>G(p.Gln174Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000108 in 1,206,297 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000092 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000011 ( 0 hom. 5 hem. )

Consequence

MID1IP1
NM_021242.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79

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=0.2247302).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MID1IP1	NM_021242.6 linkuse as main transcript	c.521A>G	p.Gln174Arg	missense_variant	3/3	ENST00000614558.3	NP_067065.1	Q9NPA3
MID1IP1	NM_001098790.2 linkuse as main transcript	c.521A>G	p.Gln174Arg	missense_variant	3/3		NP_001092260.1	Q9NPA3
MID1IP1	NM_001098791.2 linkuse as main transcript	c.521A>G	p.Gln174Arg	missense_variant	2/2		NP_001092261.1	Q9NPA3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MID1IP1	ENST00000614558.3 linkuse as main transcript	c.521A>G	p.Gln174Arg	missense_variant	3/3	5	NM_021242.6	ENSP00000483547.1	Q9NPA3
MID1IP1	ENST00000336949.7 linkuse as main transcript	c.521A>G	p.Gln174Arg	missense_variant	2/2	1		ENSP00000338706.6	Q9NPA3
MID1IP1	ENST00000378474.3 linkuse as main transcript	c.521A>G	p.Gln174Arg	missense_variant	3/3	1		ENSP00000367735.3	Q9NPA3
MID1IP1	ENST00000457894.5 linkuse as main transcript	c.521A>G	p.Gln174Arg	missense_variant	2/2	3		ENSP00000416670.1	Q9NPA3

Frequencies

GnomAD3 genomes

AF:

0.00000924

AC:

AN:

108269

Hom.:

Cov.:

AF XY:

0.0000326

AC XY:

AN XY:

30651

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:

0.0000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000442

AC:

AN:

181054

Hom.:

AF XY:

0.0000602

AC XY:

AN XY:

66452

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:

0.0000994

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1098028

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363420

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:

0.0000131

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000924

AC:

AN:

108269

Hom.:

Cov.:

AF XY:

0.0000326

AC XY:

AN XY:

30651

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:

0.0000191

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000989

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

Apr 20, 2024

The c.521A>G (p.Q174R) alteration is located in exon 2 (coding exon 1) of the MID1IP1 gene. This alteration results from a A to G substitution at nucleotide position 521, causing the glutamine (Q) at amino acid position 174 to be replaced by an arginine (R). 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

0.25

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Benign

0.79

DEOGEN2

Benign

0.052

T;T;T;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

.;T;.;.

M_CAP

Benign

0.042

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.6

.;N;N;N

REVEL

Uncertain

0.52

Sift

Benign

0.50

.;T;T;T

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.92

P;P;P;P

Vest4

0.40

MVP

0.37

MPC

0.97

ClinPred

0.47

GERP RS

5.1

Varity_R

0.25

gMVP

0.51

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