Genetic Variant MICALL1:p.Leu48Arg (chr22-37906565-T-G) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_033386.4(MICALL1):c.143T>G(p.Leu48Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MICALL1
NM_033386.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41

Publications

0 publications found

Variant links:

Genes affected

MICALL1 (HGNC:29804): (MICAL like 1) Enables identical protein binding activity; phosphatidic acid binding activity; and small GTPase binding activity. Involved in several processes, including plasma membrane tubulation; protein localization to endosome; and slow endocytic recycling. Located in late endosome and recycling endosome membrane. Is extrinsic component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MICALL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.977

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033386.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MICALL1	NM_033386.4	MANE Select	c.143T>G	p.Leu48Arg	missense	Exon 1 of 16	NP_203744.1	Q8N3F8
MICALL1	NM_001410818.1		c.143T>G	p.Leu48Arg	missense	Exon 1 of 17	NP_001397747.1	A0A7P0T9P2
MICALL1	NM_001410819.1		c.143T>G	p.Leu48Arg	missense	Exon 1 of 16	NP_001397748.1	B0QY91

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MICALL1	ENST00000215957.10	TSL:1 MANE Select	c.143T>G	p.Leu48Arg	missense	Exon 1 of 16	ENSP00000215957.6	Q8N3F8
MICALL1	ENST00000680578.1		c.143T>G	p.Leu48Arg	missense	Exon 1 of 17	ENSP00000505762.1	A0A7P0T9P2
MICALL1	ENST00000869043.1		c.143T>G	p.Leu48Arg	missense	Exon 1 of 17	ENSP00000539102.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1020476

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

481630

African (AFR)

AF:

0.00

AC:

AN:

20240

American (AMR)

AF:

0.00

AC:

AN:

6134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10952

East Asian (EAS)

AF:

0.00

AC:

AN:

19994

South Asian (SAS)

AF:

0.00

AC:

AN:

19460

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2928

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

875812

Other (OTH)

AF:

0.00

AC:

AN:

38382

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.73

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.91

MetaRNN

Pathogenic

0.98

MetaSVM

Pathogenic

0.93

MutationAssessor

Pathogenic

3.7

PhyloP100

3.4

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.8

REVEL

Pathogenic

0.84

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.68

MutPred

0.87

Gain of disorder (P = 0.023)

MVP

0.99

MPC

0.94

ClinPred

0.99

GERP RS

0.86

PromoterAI

0.018

Neutral

(source)

Varity_R

0.80

gMVP

0.57

Mutation Taster

=43/57

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over