6-31530058-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001011700.3(MCCD1):​c.*123G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000634 in 1,419,428 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000063 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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>T		3_prime_UTR	Exon 2 of 2	NP_001011700.2
	DDX39B	NM_004640.7	MANE Select	c.*376C>A		downstream_gene	N/A	NP_004631.1
	DDX39B	NM_080598.6		c.*376C>A		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>T		3_prime_UTR	Exon 2 of 2	ENSP00000365362.2
	DDX39B	ENST00000396172.6	TSL:1 MANE Select	c.*376C>A		downstream_gene	N/A	ENSP00000379475.1
	DDX39B	ENST00000458640.5	TSL:1	c.*376C>A		downstream_gene	N/A	ENSP00000416269.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152112 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000631 AC: 8 AN: 1267316 Hom.: 0 Cov.: 26 AF XY: 0.00000490 AC XY: 3 AN XY: 612226

African (AFR) AF: 0.00 AC: 0 AN: 27384

American (AMR) AF: 0.00 AC: 0 AN: 17336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18280

East Asian (EAS) AF: 0.00 AC: 0 AN: 33110

South Asian (SAS) AF: 0.00 AC: 0 AN: 57564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3504

European-Non Finnish (NFE) AF: 0.00000690 AC: 7 AN: 1015088

Other (OTH) AF: 0.0000192 AC: 1 AN: 52010

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152112 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74298

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 24835

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.73
DANN	Benign	0.52
PhyloP100		-0.46

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;