Genetic Variant MICALL2:p.Pro896Leu (chr7-1434624-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_182924.4(MICALL2):c.2687C>T(p.Pro896Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000816 in 1,588,728 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 4 hom., cov: 34)

Exomes 𝑓: 0.00043 ( 3 hom. )

Consequence

MICALL2
NM_182924.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.43

Variant links:

Genes affected

MICALL2 (HGNC:29672): (MICAL like 2) Enables filamin binding activity. Involved in positive regulation of protein targeting to mitochondrion. Predicted to be located in several cellular components, including bicellular tight junction; neuron projection; and recycling endosome. Predicted to colocalize with stress fiber. [provided by Alliance of Genome Resources, Apr 2022]

MICALL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040304065).

BP6

Variant 7-1434624-G-A is Benign according to our data. Variant chr7-1434624-G-A is described in ClinVar as [Benign]. Clinvar id is 788416.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000434 (623/1436356) while in subpopulation AFR AF= 0.0164 (522/31790). AF 95% confidence interval is 0.0153. There are 3 homozygotes in gnomad4_exome. There are 290 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICALL2	NM_182924.4 link	c.2687C>T	p.Pro896Leu	missense_variant	Exon 17 of 17	ENST00000297508.8	NP_891554.1	Q8IY33-1Q6UWK3
MICALL2	XM_047420838.1 link	c.1454C>T	p.Pro485Leu	missense_variant	Exon 11 of 11		XP_047276794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICALL2	ENST00000297508.8 link	c.2687C>T	p.Pro896Leu	missense_variant	Exon 17 of 17	1	NM_182924.4	ENSP00000297508.7		Q8IY33-1

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

675

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00129

AC:

294

AN:

227546

Hom.:

AF XY:

0.000985

AC XY:

122

AN XY:

123818

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000379

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000743

GnomAD4 exome

AF:

0.000434

AC:

623

AN:

1436356

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

290

AN XY:

713814

show subpopulations

Gnomad4 AFR exome

AF:

0.0164

Gnomad4 AMR exome

AF:

0.00149

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000364

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000272

Gnomad4 OTH exome

AF:

0.000626

GnomAD4 genome

AF:

0.00442

AC:

674

AN:

152372

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

322

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0154

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000900

Hom.:

Bravo

AF:

0.00507

ESP6500AA

AF:

0.0125

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00166

AC:

202

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.0

DANN

Benign

0.32

DEOGEN2

Benign

0.0059

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-2.0

REVEL

Benign

0.029

Sift

Benign

0.36

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.087

MVP

0.31

MPC

0.011

ClinPred

0.0025

GERP RS

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over