rs12138950

Positions:

• chr1-19512621-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The XR_947017.3(LOC105376817):​n.294-43T>G variant causes a intron, non coding transcript 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: LOC105376817 XR_947017.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

Genes affected

LOC105376819 (HGNC:):

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=-0.85).
• 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105376819	XR_007065522.1	n.311-331A>C		intron_variant, non_coding_transcript_variant
LOC105376817	XR_947017.3	n.294-43T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICOS10	ENST00000648702.1	c.-54+27966A>C		intron_variant				ENSP00000497006

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

Gnomad4 AFR AF: 0.0161

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.000583

Gnomad4 EAS AF: 0.00654

Gnomad4 SAS AF: 0.00181

Gnomad4 FIN AF: 0.000196

Gnomad4 NFE AF: 0.000556

Gnomad4 OTH AF: 0.00549

Alfa AF: 0.156 Hom.: 3156

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12138950; hg19: chr1-19839115;