ENST00000648702.1:c.-54+27966A>C

Variant names:

• chr1-19512621-A-C
• rs12138950
• ENST00000648702.1:c.-54+27966A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000648702.1(MICOS10):​c.-54+27966A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 146,418 control chromosomes in the GnomAD database, including 3 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 0.0052 (3 hom., cov: 31)
• Consequence: MICOS10 ENST00000648702.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 21 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=-0.85).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00524 (767/146418) while in subpopulation AFR AF = 0.0161 (630/39178). AF 95% confidence interval is 0.015. There are 3 homozygotes in GnomAd4. There are 378 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105376819	XR_001737920.2	n.144-5500A>C		intron_variant	Intron 1 of 2
LOC105376819	XR_007065522.1	n.311-331A>C		intron_variant	Intron 2 of 2
LOC105376817	XR_947017.3	n.294-43T>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICOS10	ENST00000648702.1	c.-54+27966A>C		intron_variant	Intron 1 of 3			ENSP00000497006.1
ENSG00000306287	ENST00000816783.1	n.523+10561T>G		intron_variant	Intron 2 of 2
ENSG00000306287	ENST00000816788.1	n.242-15283T>G		intron_variant	Intron 1 of 1
ENSG00000306287	ENST00000816790.1	n.358-15283T>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00521 AC: 763 AN: 146322 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.00680

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.000583

Gnomad EAS AF: 0.00653

Gnomad SAS AF: 0.00180

Gnomad FIN AF: 0.000196

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000556

Gnomad OTH AF: 0.00553

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

GnomAD4 genome AF: 0.00524 AC: 767 AN: 146418 Hom.: 3 Cov.: 31 AF XY: 0.00529 AC XY: 378 AN XY: 71398

African (AFR) AF: 0.0161 AC: 630 AN: 39178

American (AMR) AF: 0.00268 AC: 39 AN: 14532

Ashkenazi Jewish (ASJ) AF: 0.000583 AC: 2 AN: 3432

East Asian (EAS) AF: 0.00654 AC: 32 AN: 4890

South Asian (SAS) AF: 0.00181 AC: 8 AN: 4432

European-Finnish (FIN) AF: 0.000196 AC: 2 AN: 10228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000556 AC: 37 AN: 66558

Other (OTH) AF: 0.00549 AC: 11 AN: 2002

Alfa AF: 0.159 Hom.: 7054

Bravo AF: 0.183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.3
DANN	Benign	0.67
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs12138950; hg19: chr1-19839115;