NM_015506.3:c.*3788T>C

Variant names:

• chr1-45513003-T-C
• rs4660306
• NM_015506.3:c.*3788T>C

Variant summary

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

The NM_015506.3(MMACHC):​c.*3788T>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 0.734 in 152,056 control chromosomes in the GnomAD database, including 41,389 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 0.73 (41384 hom., cov: 31)
  • Exomes 𝑓: 0.67 (5 hom.)
• Consequence: MMACHC NM_015506.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427
• Publications: 45 publications found

Genes affected

MMACHC (HGNC:24525): (metabolism of cobalamin associated C) The exact function of the protein encoded by this gene is not known, however, its C-terminal region shows similarity to TonB, a bacterial protein involved in energy transduction for cobalamin (vitamin B12) uptake. Hence, it is postulated that this protein may have a role in the binding and intracellular trafficking of cobalamin. Mutations in this gene are associated with methylmalonic aciduria and homocystinuria type cblC. [provided by RefSeq, Oct 2009]

PRDX1 (HGNC:9352): (peroxiredoxin 1) This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein may play an antioxidant protective role in cells, and may contribute to the antiviral activity of CD8(+) T-cells. This protein may have a proliferative effect and play a role in cancer development or progression. Four transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jan 2011]

PRDX1 Gene-Disease associations (from GenCC):

• methylmalonic aciduria and homocystinuria type cblC

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015506.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMACHC	NM_015506.3	MANE Select	c.*3788T>C		3_prime_UTR	Exon 4 of 4	NP_056321.2	Q9Y4U1
	PRDX1	NM_181697.3	MANE Select	c.514+1504A>G		intron	N/A	NP_859048.1	A0A384NPQ2
	MMACHC	NM_001330540.2		c.*3788T>C		3_prime_UTR	Exon 4 of 4	NP_001317469.1	A0A0C4DGU2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMACHC	ENST00000401061.9	TSL:2 MANE Select	c.*3788T>C		3_prime_UTR	Exon 4 of 4	ENSP00000383840.4	Q9Y4U1
	PRDX1	ENST00000319248.13	TSL:1 MANE Select	c.514+1504A>G		intron	N/A	ENSP00000361152.5	Q06830
	PRDX1	ENST00000262746.5	TSL:5	c.514+1504A>G		intron	N/A	ENSP00000262746.1	Q06830

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111530 AN: 151920 Hom.: 41368 Cov.: 31

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.733

GnomAD4 exome AF: 0.667 AC: 12 AN: 18 Hom.: 5 Cov.: 0 AF XY: 0.400 AC XY: 4 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.571 AC: 8 AN: 14

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.734 AC: 111582 AN: 152038 Hom.: 41384 Cov.: 31 AF XY: 0.738 AC XY: 54825 AN XY: 74314

African (AFR) AF: 0.814 AC: 33768 AN: 41486

American (AMR) AF: 0.799 AC: 12215 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2546 AN: 3470

East Asian (EAS) AF: 0.923 AC: 4781 AN: 5178

South Asian (SAS) AF: 0.753 AC: 3627 AN: 4818

European-Finnish (FIN) AF: 0.669 AC: 7060 AN: 10554

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45122 AN: 67934

Other (OTH) AF: 0.733 AC: 1549 AN: 2112

Alfa AF: 0.698 Hom.: 62457

Bravo AF: 0.746

Asia WGS AF: 0.840 AC: 2919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.76
PhyloP100		-0.43
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: rs4660306; hg19: chr1-45978675;