1-19534612-A-G

Position:

• chr1-19534612-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000648702.1(MICOS10):​c.-54+49957A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,966 control chromosomes in the GnomAD database, including 14,655 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 0.43 (14655 hom., cov: 31)
• Consequence: MICOS10 ENST00000648702.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.793

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICOS10	ENST00000648702.1	c.-54+49957A>G		intron_variant				ENSP00000497006

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65793 AN: 151846 Hom.: 14643 Cov.: 31

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.433 AC: 65837 AN: 151966 Hom.: 14655 Cov.: 31 AF XY: 0.432 AC XY: 32095 AN XY: 74262

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.413

Alfa AF: 0.455 Hom.: 12761

Bravo AF: 0.426

Asia WGS AF: 0.335 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.1
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10917477; hg19: chr1-19861106; COSMIC: COSV71809545;