1-19534612-A-G

Variant names:

• chr1-19534612-A-G
• rs10917477
• ENST00000648702.1:c.-54+49957A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.94).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICOS10	ENST00000648702.1	c.-54+49957A>G		intron_variant	Intron 1 of 3			ENSP00000497006.1
ENSG00000306287	ENST00000816783.1	n.474-11381T>C		intron_variant	Intron 1 of 2
ENSG00000306287	ENST00000816788.1	n.241+29163T>C		intron_variant	Intron 1 of 1
ENSG00000306287	ENST00000816790.1	n.357+11423T>C		intron_variant	Intron 2 of 2

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

African (AFR) AF: 0.359 AC: 14892 AN: 41432

American (AMR) AF: 0.441 AC: 6729 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1665 AN: 3464

East Asian (EAS) AF: 0.237 AC: 1225 AN: 5166

South Asian (SAS) AF: 0.447 AC: 2157 AN: 4826

European-Finnish (FIN) AF: 0.498 AC: 5252 AN: 10538

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32575 AN: 67956

Other (OTH) AF: 0.413 AC: 873 AN: 2114

Alfa AF: 0.457 Hom.: 42399

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
PhyloP100		0.79

Splicing

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

Other links and lift over

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