Genetic Variant MID1IP1:p.Trp103Ser (chrX-38805254-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_021242.6(MID1IP1):c.308G>C(p.Trp103Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000417 in 1,198,245 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000028 ( 0 hom. 2 hem. )

Consequence

MID1IP1
NM_021242.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.25

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID1IP1	NM_021242.6 link	c.308G>C	p.Trp103Ser	missense_variant	Exon 3 of 3	ENST00000614558.3	NP_067065.1	Q9NPA3
MID1IP1	NM_001098790.2 link	c.308G>C	p.Trp103Ser	missense_variant	Exon 3 of 3		NP_001092260.1	Q9NPA3
MID1IP1	NM_001098791.2 link	c.308G>C	p.Trp103Ser	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.308G>C	p.Trp103Ser	missense_variant	Exon 3 of 3	5	NM_021242.6	ENSP00000483547.1	Q9NPA3
MID1IP1	ENST00000336949.7 link	c.308G>C	p.Trp103Ser	missense_variant	Exon 2 of 2	1		ENSP00000338706.6	Q9NPA3
MID1IP1	ENST00000378474.3 link	c.308G>C	p.Trp103Ser	missense_variant	Exon 3 of 3	1		ENSP00000367735.3	Q9NPA3
MID1IP1	ENST00000457894.5 link	c.308G>C	p.Trp103Ser	missense_variant	Exon 2 of 2	3		ENSP00000416670.1	Q9NPA3

Frequencies

GnomAD3 genomes

AF:

0.0000181

AC:

AN:

110744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32980

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:

0.000288

Gnomad SAS

AF:

0.000376

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1087501

Hom.:

Cov.:

AF XY:

0.00000563

AC XY:

AN XY:

355253

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000998

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:

0.0000181

AC:

AN:

110744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32980

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000288

Gnomad4 SAS

AF:

0.000376

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.308G>C (p.W103S) alteration is located in exon 2 (coding exon 1) of the MID1IP1 gene. This alteration results from a G to C substitution at nucleotide position 308, causing the tryptophan (W) at amino acid position 103 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

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;T;T;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

.;D;.;.

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.66

D;D;D;D

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.5

L;L;L;L

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-8.0

.;D;D;D

REVEL

Pathogenic

0.68

Sift

Pathogenic

0.0

.;D;D;D

Sift4G

Benign

0.78

T;T;T;T

Polyphen

0.98

D;D;D;D

Vest4

0.56

MutPred

0.77

Gain of disorder (P = 5e-04);Gain of disorder (P = 5e-04);Gain of disorder (P = 5e-04);Gain of disorder (P = 5e-04);

MVP

0.77

MPC

1.4

ClinPred

0.96

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.97

gMVP

0.92

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