X-38805142-C-T

Variant names:

• chrX-38805142-C-T
• rs745982845
• NM_021242.6:c.196C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_021242.6(MID1IP1):​c.196C>T​(p.Arg66Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,095,586 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 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)
  • Exomes 𝑓: 0.000016 (0 hom. 5 hem.)
• Consequence: MID1IP1 NM_021242.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00900
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22319528).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

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.196C>T	p.Arg66Cys	missense	Exon 3 of 3	NP_067065.1	Q9NPA3
	MID1IP1	NM_001098790.2		c.196C>T	p.Arg66Cys	missense	Exon 3 of 3	NP_001092260.1	Q9NPA3
	MID1IP1	NM_001098791.2		c.196C>T	p.Arg66Cys	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.196C>T	p.Arg66Cys	missense	Exon 3 of 3	ENSP00000483547.1	Q9NPA3
	MID1IP1	ENST00000336949.7	TSL:1	c.196C>T	p.Arg66Cys	missense	Exon 2 of 2	ENSP00000338706.6	Q9NPA3
	MID1IP1	ENST00000378474.3	TSL:1	c.196C>T	p.Arg66Cys	missense	Exon 3 of 3	ENSP00000367735.3	Q9NPA3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000227 AC: 4 AN: 176095 AF XY: 0.0000320

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000386

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 18 AN: 1095586 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 5 AN XY: 361352

African (AFR) AF: 0.00 AC: 0 AN: 26368

American (AMR) AF: 0.00 AC: 0 AN: 35015

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19245

East Asian (EAS) AF: 0.00 AC: 0 AN: 30167

South Asian (SAS) AF: 0.0000186 AC: 1 AN: 53753

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4119

European-Non Finnish (NFE) AF: 0.0000202 AC: 17 AN: 840767

Other (OTH) AF: 0.00 AC: 0 AN: 45970

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000247 AC: 3

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	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.0090
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.046	D
Polyphen		0.91	P
Vest4		0.32
MutPred		0.63		Loss of solvent accessibility (P = 0.0561)
MVP		0.41
MPC		0.60
ClinPred		0.27	T
GERP RS		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.18
gMVP		0.67
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

dbSNP: rs745982845; hg19: chrX-38664395;