chr1-45513003-T-C

Position:

• chr1-45513003-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMACHC	NM_015506.3	c.*3788T>C		3_prime_UTR_variant	4/4	ENST00000401061.9	NP_056321.2
PRDX1	NM_181697.3	c.514+1504A>G		intron_variant		ENST00000319248.13	NP_859048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMACHC	ENST00000401061.9	c.*3788T>C		3_prime_UTR_variant	4/4	2	NM_015506.3	ENSP00000383840.4
PRDX1	ENST00000319248.13	c.514+1504A>G		intron_variant		1	NM_181697.3	ENSP00000361152.5

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

Gnomad4 EAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 1.00

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

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.753

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.733

Alfa AF: 0.704 Hom.: 6414

Bravo AF: 0.746

Asia WGS AF: 0.840 AC: 2919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.76

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: rs4660306; hg19: chr1-45978675;