1-19516860-T-C

Variant names:

• chr1-19516860-T-C
• rs10917468
• ENST00000648702.1:c.-54+32205T>C

Variant summary

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

The ENST00000648702.1(MICOS10):​c.-54+32205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,058 control chromosomes in the GnomAD database, including 8,280 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 0.31 (8280 hom., cov: 32)
• Consequence: MICOS10 ENST00000648702.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105376819	XR_001737920.2	n.144-1261T>C		intron_variant	Intron 1 of 2
LOC105376817	XR_947017.3	n.293+1223A>G		intron_variant	Intron 3 of 3
LOC105376819	XR_947019.1	n.189-1261T>C		intron_variant	Intron 2 of 3
LOC105376819	XR_947020.3	n.144-1261T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICOS10	ENST00000648702.1	c.-54+32205T>C		intron_variant	Intron 1 of 3			ENSP00000497006.1
ENSG00000306287	ENST00000816783.1	n.523+6322A>G		intron_variant	Intron 2 of 2
ENSG00000306287	ENST00000816788.1	n.242-19522A>G		intron_variant	Intron 1 of 1
ENSG00000306287	ENST00000816790.1	n.358-19522A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47148 AN: 151940 Hom.: 8261 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.311 AC: 47221 AN: 152058 Hom.: 8280 Cov.: 32 AF XY: 0.310 AC XY: 23036 AN XY: 74340

African (AFR) AF: 0.467 AC: 19347 AN: 41442

American (AMR) AF: 0.344 AC: 5255 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3470

East Asian (EAS) AF: 0.310 AC: 1598 AN: 5150

South Asian (SAS) AF: 0.329 AC: 1587 AN: 4828

European-Finnish (FIN) AF: 0.212 AC: 2244 AN: 10580

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15403 AN: 67998

Other (OTH) AF: 0.307 AC: 647 AN: 2110

Alfa AF: 0.252 Hom.: 16020

Bravo AF: 0.324

Asia WGS AF: 0.362 AC: 1259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.30
DANN	Benign	0.52
PhyloP100		-3.3

Splicing

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

Other links and lift over

dbSNP: rs10917468; hg19: chr1-19843354;