ENST00000648702.1:c.-54+30025G>A

Variant names:

• chr1-19514680-G-A
• rs10799824
• ENST00000648702.1:c.-54+30025G>A

Variant summary

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

The ENST00000648702.1(MICOS10):​c.-54+30025G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,126 control chromosomes in the GnomAD database, including 2,585 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 0.18 (2585 hom., cov: 32)
• Consequence: MICOS10 ENST00000648702.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 28 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=-0.48).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105376819	XR_001737920.2	n.144-3441G>A		intron_variant	Intron 1 of 2
LOC105376817	XR_947017.3	n.294-2102C>T		intron_variant	Intron 3 of 3
LOC105376819	XR_947019.1	n.188+1684G>A		intron_variant	Intron 2 of 3
LOC105376819	XR_947020.3	n.144-3441G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICOS10	ENST00000648702.1	c.-54+30025G>A		intron_variant	Intron 1 of 3			ENSP00000497006.1
ENSG00000306287	ENST00000816783.1	n.523+8502C>T		intron_variant	Intron 2 of 2
ENSG00000306287	ENST00000816788.1	n.242-17342C>T		intron_variant	Intron 1 of 1
ENSG00000306287	ENST00000816790.1	n.358-17342C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26774 AN: 152008 Hom.: 2582 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.176 AC: 26801 AN: 152126 Hom.: 2585 Cov.: 32 AF XY: 0.172 AC XY: 12774 AN XY: 74366

African (AFR) AF: 0.242 AC: 10052 AN: 41472

American (AMR) AF: 0.180 AC: 2754 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 551 AN: 3470

East Asian (EAS) AF: 0.131 AC: 678 AN: 5172

South Asian (SAS) AF: 0.115 AC: 554 AN: 4822

European-Finnish (FIN) AF: 0.100 AC: 1062 AN: 10600

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10518 AN: 68004

Other (OTH) AF: 0.172 AC: 364 AN: 2112

Alfa AF: 0.161 Hom.: 8316

Bravo AF: 0.182

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.71
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs10799824; hg19: chr1-19841174;