dbSNP rs754595344: MICOS13:c.259+7C>T (chr19-5679338-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_205767.3(MICOS13):c.259+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MICOS13
NM_205767.3 splice_region, intron

Scores

Splicing: ADA: 0.00006589

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.270

Publications

0 publications found

Variant links:

Genes affected

MICOS13 (HGNC:33702): (mitochondrial contact site and cristae organizing system subunit 13) Involved in cristae formation. Located in mitochondrial crista junction and nucleoplasm. Part of MICOS complex. Implicated in combined oxidative phosphorylation deficiency 37. [provided by Alliance of Genome Resources, Apr 2022]

MICOS13 links:

RPL36 (HGNC:13631): (ribosomal protein L36) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L36E family of ribosomal proteins. It is located in the cytoplasm. Transcript variants derived from alternative splicing exist; they encode the same protein. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPL36 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205767.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MICOS13	NM_205767.3	MANE Select	c.259+7C>T	splice_region intron	N/A	NP_991330.1	Q5XKP0
MICOS13	NM_001308240.2		c.325+7C>T	splice_region intron	N/A	NP_001295169.1	A0A140TA86
MICOS13	NM_001365761.2		c.325+7C>T	splice_region intron	N/A	NP_001352690.1	A0A140TA86

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MICOS13	ENST00000309324.9	TSL:1 MANE Select	c.259+7C>T	splice_region intron	N/A	ENSP00000309561.3	Q5XKP0
MICOS13	ENST00000587950.5	TSL:2	c.325+7C>T	splice_region intron	N/A	ENSP00000468723.1	A0A140TA86
MICOS13	ENST00000896351.1		c.286+7C>T	splice_region intron	N/A	ENSP00000566410.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000804

AC:

AN:

248804

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000584

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460188

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726402

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.0000449

AC:

AN:

44546

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111024

Other (OTH)

AF:

0.00

AC:

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.6

(source)

DANN

Benign

0.63

PhyloP100

-0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000066

dbscSNV1_RF

Benign

0.046

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over