6-31530198-T-C

Variant names:

• chr6-31530198-T-C
• rs3219190
• NM_001011700.3:c.*263T>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.*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
• Publications: 22 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=-0.61).
• 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

African (AFR) AF: 0.0156 AC: 241 AN: 15434

American (AMR) AF: 0.0554 AC: 957 AN: 17278

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 1970 AN: 14464

East Asian (EAS) AF: 0.00342 AC: 107 AN: 31274

South Asian (SAS) AF: 0.0356 AC: 1627 AN: 45716

European-Finnish (FIN) AF: 0.127 AC: 4660 AN: 36802

Middle Eastern (MID) AF: 0.107 AC: 246 AN: 2292

European-Non Finnish (NFE) AF: 0.115 AC: 49936 AN: 435156

Other (OTH) AF: 0.101 AC: 3158 AN: 31422

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

African (AFR) AF: 0.0208 AC: 864 AN: 41474

American (AMR) AF: 0.0640 AC: 978 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3468

East Asian (EAS) AF: 0.00562 AC: 29 AN: 5164

South Asian (SAS) AF: 0.0322 AC: 155 AN: 4814

European-Finnish (FIN) AF: 0.121 AC: 1280 AN: 10550

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7656 AN: 67944

Other (OTH) AF: 0.0689 AC: 145 AN: 2106

Alfa AF: 0.0946 Hom.: 2159

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
PhyloP100		-1.7
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: rs3219190; hg19: chr6-31497975;