NM_001093.4:c.-10+3688T>C

Variant names:

• chr12-109120392-T-C
• rs246085
• NM_001093.4:c.-10+3688T>C

Variant summary

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

The NM_001093.4(ACACB):​c.-10+3688T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,118 control chromosomes in the GnomAD database, including 1,792 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 0.12 (1792 hom., cov: 32)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 5 publications found

Genes affected

ACACB (HGNC:85): (acetyl-CoA carboxylase beta) Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. ACC-beta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine-palmitoyl-CoA transferase I, the rate-limiting step in fatty acid uptake and oxidation by mitochondria. ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. [provided by RefSeq, Oct 2022]

UNG (HGNC:12572): (uracil DNA glycosylase) This gene encodes one of several uracil-DNA glycosylases. One important function of uracil-DNA glycosylases is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosylic bond and initiating the base-excision repair (BER) pathway. Uracil bases occur from cytosine deamination or misincorporation of dUMP residues. Alternative promoter usage and splicing of this gene leads to two different isoforms: the mitochondrial UNG1 and the nuclear UNG2. The UNG2 term was used as a previous symbol for the CCNO gene (GeneID 10309), which has been confused with this gene, in the literature and some databases. [provided by RefSeq, Nov 2010]

UNG Gene-Disease associations (from GenCC):

• hyper-IgM syndrome type 5

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ENSG00000256139 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.-10+3688T>C		intron_variant	Intron 1 of 52	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.-10+3688T>C		intron_variant	Intron 1 of 52	1	NM_001093.4	ENSP00000341044.7
UNG	ENST00000699563.1	c.775-5553T>C		intron_variant	Intron 5 of 5			ENSP00000514437.1
ENSG00000256139	ENST00000541704.2	n.577-4869T>C		intron_variant	Intron 2 of 2	5
ENSG00000256139	ENST00000755021.1	n.486-3482T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18358 AN: 152000 Hom.: 1788 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.0663

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.0922

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.121 AC: 18387 AN: 152118 Hom.: 1792 Cov.: 32 AF XY: 0.118 AC XY: 8752 AN XY: 74364

African (AFR) AF: 0.268 AC: 11095 AN: 41430

American (AMR) AF: 0.0663 AC: 1013 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 212 AN: 3470

East Asian (EAS) AF: 0.0641 AC: 332 AN: 5176

South Asian (SAS) AF: 0.0923 AC: 445 AN: 4820

European-Finnish (FIN) AF: 0.0585 AC: 621 AN: 10612

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0646 AC: 4395 AN: 68004

Other (OTH) AF: 0.103 AC: 217 AN: 2114

Alfa AF: 0.0877 Hom.: 2365

Bravo AF: 0.126

Asia WGS AF: 0.0890 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.1
DANN	Benign	0.82
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs246085; hg19: chr12-109558197;