22-37911995-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_033386.4(MICALL1):​c.190C>T​(p.Arg64Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R64H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MICALL1
NM_033386.4 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MICALL1NM_033386.4 linkc.190C>T p.Arg64Cys missense_variant Exon 2 of 16 ENST00000215957.10 NP_203744.1 Q8N3F8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MICALL1ENST00000215957.10 linkc.190C>T p.Arg64Cys missense_variant Exon 2 of 16 1 NM_033386.4 ENSP00000215957.6 Q8N3F8

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152086
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251452
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461872
Hom.:
0
Cov.:
33
AF XY:
0.0000206
AC XY:
15
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000150
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152204
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.190C>T (p.R64C) alteration is located in exon 2 (coding exon 2) of the MICALL1 gene. This alteration results from a C to T substitution at nucleotide position 190, causing the arginine (R) at amino acid position 64 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.72
D
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.96
D
M_CAP
Pathogenic
0.46
D
MetaRNN
Pathogenic
0.78
D
MetaSVM
Pathogenic
0.89
D
MutationAssessor
Benign
2.0
M
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-5.2
D
REVEL
Pathogenic
0.74
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0040
D
Polyphen
1.0
D
Vest4
0.63
MutPred
0.57
Gain of catalytic residue at L65 (P = 0.015);
MVP
0.97
MPC
0.84
ClinPred
0.72
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.39
gMVP
0.33

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: rs576976408; hg19: chr22-38308002; API