X-38805284-C-G

Variant names:

• chrX-38805284-C-G
• NM_021242.6:c.338C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021242.6(MID1IP1):​c.338C>G​(p.Ala113Gly) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A113S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: MID1IP1 NM_021242.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05229178).

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.338C>G	p.Ala113Gly	missense	Exon 3 of 3	NP_067065.1	Q9NPA3
	MID1IP1	NM_001098790.2		c.338C>G	p.Ala113Gly	missense	Exon 3 of 3	NP_001092260.1	Q9NPA3
	MID1IP1	NM_001098791.2		c.338C>G	p.Ala113Gly	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.338C>G	p.Ala113Gly	missense	Exon 3 of 3	ENSP00000483547.1	Q9NPA3
	MID1IP1	ENST00000336949.7	TSL:1	c.338C>G	p.Ala113Gly	missense	Exon 2 of 2	ENSP00000338706.6	Q9NPA3
	MID1IP1	ENST00000378474.3	TSL:1	c.338C>G	p.Ala113Gly	missense	Exon 3 of 3	ENSP00000367735.3	Q9NPA3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

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	0.067
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.83
DEOGEN2	Benign	0.020	T
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.72	N
PhyloP100		1.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.069
Sift	Benign	1.0	T
Sift4G	Benign	0.78	T
Polyphen		0.0060	B
Vest4		0.13
MutPred		0.40		Loss of loop (P = 0.0603)
MVP		0.25
MPC		0.34
ClinPred		0.052	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.088
gMVP		0.28
Mutation Taster		=97/3	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-38664537;