Genetic Variant MICALL1:p.Ser29Asn (chr22-37906508-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_033386.4(MICALL1):c.86G>A(p.Ser29Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000876 in 1,255,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

MICALL1
NM_033386.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

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]

MICALL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.409361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICALL1	NM_033386.4 link	c.86G>A	p.Ser29Asn	missense_variant	Exon 1 of 16	ENST00000215957.10	NP_203744.1	Q8N3F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICALL1	ENST00000215957.10 link	c.86G>A	p.Ser29Asn	missense_variant	Exon 1 of 16	1	NM_033386.4	ENSP00000215957.6		Q8N3F8

Frequencies

GnomAD3 genomes

AF:

0.0000466

AC:

AN:

150244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000362

AC:

AN:

1104932

Hom.:

Cov.:

AF XY:

0.00000561

AC XY:

AN XY:

534386

show subpopulations

Gnomad4 AFR exome

AF:

0.0000447

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000286

Gnomad4 FIN exome

AF:

0.0000332

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000236

GnomAD4 genome

AF:

0.0000466

AC:

AN:

150244

Hom.:

Cov.:

AF XY:

0.0000819

AC XY:

AN XY:

73302

show subpopulations

Gnomad4 AFR

AF:

0.000170

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.86G>A (p.S29N) alteration is located in exon 1 (coding exon 1) of the MICALL1 gene. This alteration results from a G to A substitution at nucleotide position 86, causing the serine (S) at amino acid position 29 to be replaced by an asparagine (N). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.00099

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

Eigen

Benign

-0.022

Eigen_PC

Benign

-0.066

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.41

MetaSVM

Uncertain

0.67

MutationAssessor

Benign

1.2

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.45

Sift

Uncertain

0.029

Sift4G

Benign

0.066

Polyphen

0.67

Vest4

0.22

MutPred

0.48

Loss of disorder (P = 0.0972);

MVP

0.92

MPC

0.32

ClinPred

0.12

GERP RS

2.4

Varity_R

0.19

gMVP

0.18

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