X-38805271-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021242.6(MID1IP1):c.325C>T(p.Pro109Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000501 in 1,198,023 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

MID1IP1
NM_021242.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0666897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID1IP1	NM_021242.6 link	c.325C>T	p.Pro109Ser	missense_variant	Exon 3 of 3	ENST00000614558.3	NP_067065.1	Q9NPA3
MID1IP1	NM_001098790.2 link	c.325C>T	p.Pro109Ser	missense_variant	Exon 3 of 3		NP_001092260.1	Q9NPA3
MID1IP1	NM_001098791.2 link	c.325C>T	p.Pro109Ser	missense_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.325C>T	p.Pro109Ser	missense_variant	Exon 3 of 3	5	NM_021242.6	ENSP00000483547.1	Q9NPA3
MID1IP1	ENST00000336949.7 link	c.325C>T	p.Pro109Ser	missense_variant	Exon 2 of 2	1		ENSP00000338706.6	Q9NPA3
MID1IP1	ENST00000378474.3 link	c.325C>T	p.Pro109Ser	missense_variant	Exon 3 of 3	1		ENSP00000367735.3	Q9NPA3
MID1IP1	ENST00000457894.5 link	c.325C>T	p.Pro109Ser	missense_variant	Exon 2 of 2	3		ENSP00000416670.1	Q9NPA3

Frequencies

GnomAD3 genomes

AF:

0.0000361

AC:

AN:

110666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32900

show subpopulations

Gnomad AFR

AF:

0.0000988

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:

0.00

Gnomad OTH

AF:

0.000670

GnomAD3 exomes

AF:

0.0000179

AC:

AN:

167896

Hom.:

AF XY:

0.00

AC XY:

AN XY:

57044

show subpopulations

Gnomad AFR exome

AF:

0.000240

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000184

AC:

AN:

1087357

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

355317

show subpopulations

Gnomad4 AFR exome

AF:

0.0000762

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000361

AC:

AN:

110666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32900

show subpopulations

Gnomad4 AFR

AF:

0.0000988

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:

0.00

Gnomad4 OTH

AF:

0.000670

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.325C>T (p.P109S) 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 325, causing the proline (P) at amino acid position 109 to be replaced by a serine (S). 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

0.071

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0092

T;T;T;T

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.57

.;T;.;.

M_CAP

Benign

0.033

MetaRNN

Benign

0.067

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.26

.;N;N;N

REVEL

Benign

0.047

Sift

Benign

0.27

.;T;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.0030

B;B;B;B

Vest4

0.22

MVP

0.46

MPC

0.60

ClinPred

0.031

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.080

gMVP

0.37

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