NM_021242.6:c.227C>T

Variant names:

• chrX-38805173-C-T
• NM_021242.6:c.227C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/20 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
• Publications: 0 publications found

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-AS1 (HGNC:40932): (MID1IP1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021242.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MID1IP1	NM_021242.6	MANE Select	c.227C>T	p.Ala76Val	missense	Exon 3 of 3	NP_067065.1	Q9NPA3
	MID1IP1	NM_001098790.2		c.227C>T	p.Ala76Val	missense	Exon 3 of 3	NP_001092260.1	Q9NPA3
	MID1IP1	NM_001098791.2		c.227C>T	p.Ala76Val	missense	Exon 2 of 2	NP_001092261.1	Q9NPA3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MID1IP1	ENST00000614558.3	TSL:5 MANE Select	c.227C>T	p.Ala76Val	missense	Exon 3 of 3	ENSP00000483547.1	Q9NPA3
	MID1IP1	ENST00000336949.7	TSL:1	c.227C>T	p.Ala76Val	missense	Exon 2 of 2	ENSP00000338706.6	Q9NPA3
	MID1IP1	ENST00000378474.3	TSL:1	c.227C>T	p.Ala76Val	missense	Exon 3 of 3	ENSP00000367735.3	Q9NPA3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.82
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.13
Sift	Benign	0.34	T
Sift4G	Benign	0.43	T
Polyphen		0.094	B
Vest4		0.065
MutPred		0.63		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
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

hg19: chrX-38664426;