X-38805243-C-G

Position:

• chrX-38805243-C-G

Variant summary

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

The NM_021242.6(MID1IP1):​c.297C>G​(p.Asn99Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: MID1IP1 NM_021242.6 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.887

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MID1IP1	NM_021242.6	c.297C>G	p.Asn99Lys	missense_variant	3/3	ENST00000614558.3
MID1IP1	NM_001098790.2	c.297C>G	p.Asn99Lys	missense_variant	3/3
MID1IP1	NM_001098791.2	c.297C>G	p.Asn99Lys	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MID1IP1	ENST00000614558.3	c.297C>G	p.Asn99Lys	missense_variant	3/3	5	NM_021242.6	P1
MID1IP1	ENST00000336949.7	c.297C>G	p.Asn99Lys	missense_variant	2/2	1		P1
MID1IP1	ENST00000378474.3	c.297C>G	p.Asn99Lys	missense_variant	3/3	1		P1
MID1IP1	ENST00000457894.5	c.297C>G	p.Asn99Lys	missense_variant	2/2	3		P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Flexion contracture Uncertain:1

Uncertain significance, no assertion criteria provided

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;T;T
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.6	M;M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.85	D
Sift4G	Benign	0.088	T;T;T;T
Polyphen		0.98	D;D;D;D
Vest4		0.57
MutPred		0.69		Loss of stability (P = 0.0072);Loss of stability (P = 0.0072);Loss of stability (P = 0.0072);Loss of stability (P = 0.0072);
MVP		0.46
MPC		1.0
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.70
gMVP		0.81

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

Other links and lift over

dbSNP: rs1602158924; hg19: chrX-38664496;