Variant 7-1434651-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182924.4(MICALL2):c.2660A>C(p.Lys887Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,567,926 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 10 hom., cov: 34)

Exomes 𝑓: 0.0044 ( 50 hom. )

Consequence

MICALL2
NM_182924.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.513

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042794943).

BP6

Variant 7-1434651-T-G is Benign according to our data. Variant chr7-1434651-T-G is described in ClinVar as [Benign]. Clinvar id is 781891.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00437 (6192/1415564) while in subpopulation MID AF= 0.0215 (119/5542). AF 95% confidence interval is 0.0183. There are 50 homozygotes in gnomad4_exome. There are 3402 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICALL2	NM_182924.4 linkuse as main transcript	c.2660A>C	p.Lys887Thr	missense_variant	17/17	ENST00000297508.8	NP_891554.1
MICALL2	XM_047420838.1 linkuse as main transcript	c.1427A>C	p.Lys476Thr	missense_variant	11/11		XP_047276794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICALL2	ENST00000297508.8 linkuse as main transcript	c.2660A>C	p.Lys887Thr	missense_variant	17/17	1	NM_182924.4	ENSP00000297508	P1	Q8IY33-1

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

575

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0167

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00342

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00670

AC:

1431

AN:

213670

Hom.:

AF XY:

0.00740

AC XY:

861

AN XY:

116334

show subpopulations

Gnomad AFR exome

AF:

0.000256

Gnomad AMR exome

AF:

0.00429

Gnomad ASJ exome

AF:

0.0591

Gnomad EAS exome

AF:

0.0000619

Gnomad SAS exome

AF:

0.0175

Gnomad FIN exome

AF:

0.000152

Gnomad NFE exome

AF:

0.00410

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.00437

AC:

6192

AN:

1415564

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

3402

AN XY:

701244

show subpopulations

Gnomad4 AFR exome

AF:

0.000936

Gnomad4 AMR exome

AF:

0.00443

Gnomad4 ASJ exome

AF:

0.0545

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0163

Gnomad4 FIN exome

AF:

0.000231

Gnomad4 NFE exome

AF:

0.00263

Gnomad4 OTH exome

AF:

0.00715

GnomAD4 genome

AF:

0.00377

AC:

575

AN:

152362

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

288

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.0527

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00343

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00652

Hom.:

Bravo

AF:

0.00365

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00558

AC:

ExAC

AF:

0.00734

AC:

891

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.77

D;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.072

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.032

Polyphen

0.97

Vest4

0.33

MVP

0.81

MPC

0.056

ClinPred

0.043

GERP RS

0.53

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.4

Varity_R

0.13

gMVP

0.50

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

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