rs12084204

Variant names:

• chr1-19506073-C-T
• rs12084204
• ENST00000648702.1:c.-54+21418C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000648702.1(MICOS10):​c.-54+21418C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,098 control chromosomes in the GnomAD database, including 7,308 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7308 hom., cov: 33)
• Consequence: MICOS10 ENST00000648702.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 2 publications found

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]

ENSG00000306287 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105376819	XR_001737920.2	n.143+5710C>T		intron_variant	Intron 1 of 2
LOC105376819	XR_007065522.1	n.310+5710C>T		intron_variant	Intron 2 of 2
LOC105376819	XR_947019.1	n.143+5710C>T		intron_variant	Intron 1 of 3
LOC105376819	XR_947020.3	n.143+5710C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICOS10	ENST00000648702.1	c.-54+21418C>T		intron_variant	Intron 1 of 3			ENSP00000497006.1
ENSG00000306287	ENST00000816783.1	n.524-8735G>A		intron_variant	Intron 2 of 2
ENSG00000306287	ENST00000816788.1	n.242-8735G>A		intron_variant	Intron 1 of 1
ENSG00000306287	ENST00000816790.1	n.358-8735G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45630 AN: 151980 Hom.: 7311 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.318

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.300 AC: 45645 AN: 152098 Hom.: 7308 Cov.: 33 AF XY: 0.306 AC XY: 22749 AN XY: 74352

African (AFR) AF: 0.203 AC: 8428 AN: 41510

American (AMR) AF: 0.307 AC: 4685 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3468

East Asian (EAS) AF: 0.537 AC: 2777 AN: 5170

South Asian (SAS) AF: 0.418 AC: 2012 AN: 4818

European-Finnish (FIN) AF: 0.362 AC: 3823 AN: 10566

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21752 AN: 67970

Other (OTH) AF: 0.321 AC: 678 AN: 2110

Alfa AF: 0.310 Hom.: 12150

Bravo AF: 0.293

Asia WGS AF: 0.433 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs12084204; hg19: chr1-19832567;