6-31530198-T-C

Variant names:

• chr6-31530198-T-C
• rs3219190
• NM_001011700.3:c.*263T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001011700.3(MCCD1):​c.*263T>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 0.0954 in 781,844 control chromosomes in the GnomAD database, including 4,309 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 0.077 (609 hom., cov: 31)
  • Exomes 𝑓: 0.10 (3700 hom.)
• Consequence: MCCD1 NM_001011700.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCCD1	NM_001011700.3	c.*263T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000376191.3	NP_001011700.2
DDX39B	NM_004640.7	c.*236A>G		downstream_gene_variant		ENST00000396172.6	NP_004631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCCD1	ENST00000376191.3	c.*263T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_001011700.3	ENSP00000365362.2
DDX39B	ENST00000396172.6	c.*236A>G		downstream_gene_variant		1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*1737A>G		downstream_gene_variant		2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.0770 AC: 11694 AN: 151888 Hom.: 611 Cov.: 31

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0641

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.00560

Gnomad SAS AF: 0.0318

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0691

GnomAD4 exome AF: 0.0999 AC: 62902 AN: 629838 Hom.: 3700 Cov.: 8 AF XY: 0.0977 AC XY: 31314 AN XY: 320584

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.0554

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.00342

Gnomad4 SAS exome AF: 0.0356

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.0769 AC: 11691 AN: 152006 Hom.: 609 Cov.: 31 AF XY: 0.0760 AC XY: 5647 AN XY: 74282

Gnomad4 AFR AF: 0.0208

Gnomad4 AMR AF: 0.0640

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.00562

Gnomad4 SAS AF: 0.0322

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0689

Alfa AF: 0.102 Hom.: 636

Bravo AF: 0.0714

Asia WGS AF: 0.0270 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.1
DANN	Benign	0.89

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: rs3219190; hg19: chr6-31497975;