chr6-31530058-G-C

Variant names:

• chr6-31530058-G-C
• rs3115537
• NM_001011700.3:c.*123G>C

Variant summary

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

The NM_001011700.3(MCCD1):​c.*123G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,418,310 control chromosomes in the GnomAD database, including 482,797 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 0.85 (54747 hom., cov: 31)
  • Exomes 𝑓: 0.82 (428050 hom.)
• Consequence: MCCD1 NM_001011700.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463
• Publications: 25 publications found

Genes affected

MCCD1 (HGNC:20668): (mitochondrial coiled-coil domain 1) Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

DDX39B (HGNC:13917): (DExD-box helicase 39B) This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and it also plays an important role in mRNA export from the nucleus to the cytoplasm. This gene belongs to a cluster of genes localized in the vicinity of the genes encoding tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on both chromosomes 6 and 11. Read-through transcription also occurs between this gene and the upstream ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) gene. [provided by RefSeq, Feb 2011]

ATP6V1G2-DDX39B (HGNC:41999): (ATP6V1G2-DDX39B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) and DDX39B (DEAD box polypeptide 39B) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript and is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011700.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCCD1	NM_001011700.3	MANE Select	c.*123G>C		3_prime_UTR	Exon 2 of 2	NP_001011700.2
	DDX39B	NM_004640.7	MANE Select	c.*376C>G		downstream_gene	N/A	NP_004631.1
	DDX39B	NM_080598.6		c.*376C>G		downstream_gene	N/A	NP_542165.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCCD1	ENST00000376191.3	TSL:1 MANE Select	c.*123G>C		3_prime_UTR	Exon 2 of 2	ENSP00000365362.2
	DDX39B	ENST00000396172.6	TSL:1 MANE Select	c.*376C>G		downstream_gene	N/A	ENSP00000379475.1
	DDX39B	ENST00000458640.5	TSL:1	c.*376C>G		downstream_gene	N/A	ENSP00000416269.1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128849 AN: 152078 Hom.: 54690 Cov.: 31

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.859

GnomAD4 exome AF: 0.821 AC: 1039673 AN: 1266114 Hom.: 428050 Cov.: 26 AF XY: 0.824 AC XY: 504176 AN XY: 611694

African (AFR) AF: 0.886 AC: 24250 AN: 27376

American (AMR) AF: 0.876 AC: 15169 AN: 17322

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 17153 AN: 18272

East Asian (EAS) AF: 0.919 AC: 30434 AN: 33104

South Asian (SAS) AF: 0.925 AC: 53230 AN: 57532

European-Finnish (FIN) AF: 0.814 AC: 34990 AN: 42990

Middle Eastern (MID) AF: 0.911 AC: 3190 AN: 3502

European-Non Finnish (NFE) AF: 0.807 AC: 817936 AN: 1014034

Other (OTH) AF: 0.833 AC: 43321 AN: 51982

GnomAD4 genome AF: 0.847 AC: 128964 AN: 152196 Hom.: 54747 Cov.: 31 AF XY: 0.852 AC XY: 63362 AN XY: 74406

African (AFR) AF: 0.876 AC: 36367 AN: 41520

American (AMR) AF: 0.868 AC: 13272 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3263 AN: 3470

East Asian (EAS) AF: 0.926 AC: 4794 AN: 5176

South Asian (SAS) AF: 0.923 AC: 4461 AN: 4832

European-Finnish (FIN) AF: 0.824 AC: 8741 AN: 10602

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55227 AN: 67990

Other (OTH) AF: 0.860 AC: 1819 AN: 2114

Alfa AF: 0.822 Hom.: 24835

Bravo AF: 0.851

Asia WGS AF: 0.865 AC: 3011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.78
DANN	Benign	0.44
PhyloP100		-0.46
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: rs3115537; hg19: chr6-31497835;