7-1436770-C-T

Variant summary

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

The NM_182924.4(MICALL2):​c.2563G>A​(p.Val855Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,455,590 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V855L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MICALL2
NM_182924.4 missense

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.835
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
MICALL2NM_182924.4 linkc.2563G>A p.Val855Met missense_variant Exon 15 of 17 ENST00000297508.8 NP_891554.1 Q8IY33-1Q6UWK3
MICALL2XM_047420838.1 linkc.1330G>A p.Val444Met missense_variant Exon 9 of 11 XP_047276794.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MICALL2ENST00000297508.8 linkc.2563G>A p.Val855Met missense_variant Exon 15 of 17 1 NM_182924.4 ENSP00000297508.7 Q8IY33-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000832
AC:
2
AN:
240296
Hom.:
0
AF XY:
0.00000763
AC XY:
1
AN XY:
131134
show subpopulations
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 SAS exome
AF:
0.0000332
Gnomad FIN exome
AF:
0.0000486
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000344
AC:
5
AN:
1455590
Hom.:
0
Cov.:
31
AF XY:
0.00000414
AC XY:
3
AN XY:
724218
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000255
Gnomad4 SAS exome
AF:
0.0000349
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.40
BayesDel_addAF
Benign
-0.070
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.39
FATHMM_MKL
Benign
0.33
N
LIST_S2
Uncertain
0.93
D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.58
D
MetaSVM
Benign
-0.32
T
MutationAssessor
Pathogenic
3.5
M
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.26
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.48
MVP
0.61
MPC
0.073
ClinPred
0.73
D
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.15
gMVP
0.49

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.

Other links and lift over

dbSNP: rs200767614; hg19: chr7-1476406; API