6-33700188-G-T

Position:

• chr6-33700188-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032340.4(UQCC2):​c.283+256C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,128 control chromosomes in the GnomAD database, including 45,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.75 (45379 hom., cov: 33)
• Consequence: UQCC2 NM_032340.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90

Genes affected

UQCC2 (HGNC:21237): (ubiquinol-cytochrome c reductase complex assembly factor 2) This gene encodes a nucleoid protein localized to the mitochondria inner membrane. The encoded protein affects regulation of insulin secretion, mitochondrial ATP production, and myogenesis through modulation of mitochondrial respiratory chain activity. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-33700188-G-T is Benign according to our data. Variant chr6-33700188-G-T is described in ClinVar as [Benign]. Clinvar id is 669588.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UQCC2	NM_032340.4	c.283+256C>A		intron_variant		ENST00000607484.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UQCC2	ENST00000607484.6	c.283+256C>A		intron_variant		1	NM_032340.4	P1
UQCC2	ENST00000374214.3	c.208+256C>A		intron_variant		5
UQCC2	ENST00000374231.8	c.281+256C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114215 AN: 152010 Hom.: 45371 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.751 AC: 114262 AN: 152128 Hom.: 45379 Cov.: 33 AF XY: 0.762 AC XY: 56665 AN XY: 74374

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.923

Gnomad4 NFE AF: 0.847

Gnomad4 OTH AF: 0.760

Alfa AF: 0.833 Hom.: 75524

Bravo AF: 0.733

Asia WGS AF: 0.857 AC: 2981 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs594223; hg19: chr6-33667965;