NM_001032363.4:c.62T>C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001032363.4(MICOS10):c.62T>C(p.Ile21Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000744 in 1,599,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

MICOS10
NM_001032363.4 missense, splice_region

Scores

Splicing: ADA: 0.0007140

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.22

Publications

0 publications found

Variant links:

Genes affected

MICOS10 (HGNC:32068): (mitochondrial contact site and cristae organizing system subunit 10) Predicted to be involved in inner mitochondrial membrane organization. Located in mitochondrion. Part of MIB complex; MICOS complex; and SAM complex. [provided by Alliance of Genome Resources, Apr 2022]

MICOS10 links:

MICOS10-NBL1 (HGNC:48338): (MICOS10-NBL1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring chromosome 1 open reading frame 151 (GeneID 440574) and neuroblastoma suppressor of tumorigenicity 1 (GeneID 4681) genes on chromosome 1. The read-through transcripts produce at least two proteins, each of which share identity with proteins translated from the downstream neuroblastoma suppressor of tumorigenicity 1 locus. [provided by RefSeq, Feb 2011]

MICOS10-NBL1 links:

NBL1 (HGNC:7650): (NBL1, DAN family BMP antagonist) This gene product is the founding member of the evolutionarily conserved CAN (Cerberus and DAN) family of proteins, which contain a domain resembling the CTCK (C-terminal cystine knot-like) motif found in a number of signaling molecules. These proteins are secreted, and act as BMP (bone morphogenetic protein) antagonists by binding to BMPs and preventing them from interacting with their receptors. They may thus play an important role during growth and development. Alternatively spliced transcript variants have been identified for this gene. Read-through transcripts between this locus and the upstream mitochondrial inner membrane organizing system 1 gene (GeneID 440574) have been observed. [provided by RefSeq, May 2013]

NBL1 links:

MICOS10-DT (HGNC:55676): (MICOS10 divergent transcript)

MICOS10-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39747852).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032363.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MICOS10	NM_001032363.4	MANE Select	c.62T>C	p.Ile21Thr	missense splice_region	Exon 1 of 4	NP_001027535.1	Q5TGZ0-1
MICOS10-NBL1	NM_001204088.2		c.-165T>C		splice_region	Exon 1 of 5	NP_001191017.1
MICOS10-NBL1	NM_001204089.2		c.-22T>C		splice_region	Exon 1 of 4	NP_001191018.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MICOS10	ENST00000322753.7	TSL:1 MANE Select	c.62T>C	p.Ile21Thr	missense splice_region	Exon 1 of 4	ENSP00000325562.6	Q5TGZ0-1
MICOS10-NBL1	ENST00000602384.5	TSL:5	n.41T>C		splice_region non_coding_transcript_exon	Exon 1 of 10	ENSP00000473550.1	R4GNA1
NBL1	ENST00000602662.1	TSL:2	c.-22T>C		splice_region	Exon 1 of 4	ENSP00000473411.1	P41271-1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000551

AC:

AN:

235926

AF XY:

0.0000389

show subpopulations

Gnomad AFR exome

AF:

0.0000695

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000628

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000801

AC:

116

AN:

1447776

Hom.:

Cov.:

AF XY:

0.0000791

AC XY:

AN XY:

720258

show subpopulations

African (AFR)

AF:

0.0000314

AC:

AN:

31894

American (AMR)

AF:

0.00

AC:

AN:

43078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25678

East Asian (EAS)

AF:

0.00

AC:

AN:

37432

South Asian (SAS)

AF:

0.00

AC:

AN:

84914

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.000101

AC:

112

AN:

1105984

Other (OTH)

AF:

0.0000167

AC:

AN:

59820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151874

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41346

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67964

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0076

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.50

M_CAP

Benign

0.015

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.96

PhyloP100

4.2

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.61

REVEL

Benign

0.067

Sift

Benign

0.45

Sift4G

Benign

0.16

Polyphen

0.0

Vest4

0.63

MVP

0.48

MPC

0.047

ClinPred

0.49

GERP RS

5.2

PromoterAI

-0.090

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.13

gMVP

0.48

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00071

dbscSNV1_RF

Benign

0.018

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over