X-38805173-C-T

Position:

• chrX-38805173-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021242.6(MID1IP1):​c.227C>T​(p.Ala76Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 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)
• Consequence: MID1IP1 NM_021242.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.823

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12881196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MID1IP1	NM_021242.6	c.227C>T	p.Ala76Val	missense_variant	3/3	ENST00000614558.3
MID1IP1	NM_001098790.2	c.227C>T	p.Ala76Val	missense_variant	3/3
MID1IP1	NM_001098791.2	c.227C>T	p.Ala76Val	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MID1IP1	ENST00000614558.3	c.227C>T	p.Ala76Val	missense_variant	3/3	5	NM_021242.6	P1
MID1IP1	ENST00000336949.7	c.227C>T	p.Ala76Val	missense_variant	2/2	1		P1
MID1IP1	ENST00000378474.3	c.227C>T	p.Ala76Val	missense_variant	3/3	1		P1
MID1IP1	ENST00000457894.5	c.227C>T	p.Ala76Val	missense_variant	2/2	3		P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.227C>T (p.A76V) 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 227, causing the alanine (A) at amino acid position 76 to be replaced by a valine (V). 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	0.089
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T;T;T;T
FATHMM_MKL	Benign	0.72	D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.2	L;L;L;L
MutationTaster	Benign	0.85	D;D;D
PrimateAI	Uncertain	0.63	T
Sift4G	Benign	0.43	T;T;T;T
Polyphen		0.094	B;B;B;B
Vest4		0.065
MutPred		0.63		Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);
MVP		0.49
MPC		0.35
ClinPred		0.22	T
GERP RS		3.8
Varity_R		0.18
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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-38664426;