chr1-45511371-A-G

Variant names:

• chr1-45511371-A-G
• NM_181697.3:c.558T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_181697.3(PRDX1):​c.558T>C​(p.Pro186Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: PRDX1 NM_181697.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.728
• Publications: 0 publications found

Genes affected

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]

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]

MMACHC Gene-Disease associations (from GenCC):

• methylmalonic aciduria and homocystinuria type cblC

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Myriad Women’s Health, ClinGen, G2P, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 1-45511371-A-G is Benign according to our data. Variant chr1-45511371-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1665330.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.728 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX1	NM_181697.3	c.558T>C	p.Pro186Pro	synonymous_variant	Exon 6 of 6	ENST00000319248.13	NP_859048.1
MMACHC	NM_015506.3	c.*2156A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000401061.9	NP_056321.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX1	ENST00000319248.13	c.558T>C	p.Pro186Pro	synonymous_variant	Exon 6 of 6	1	NM_181697.3	ENSP00000361152.5
MMACHC	ENST00000401061.9	c.*2156A>G		3_prime_UTR_variant	Exon 4 of 4	2	NM_015506.3	ENSP00000383840.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1460866 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726728

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111612

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 15, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		0.73
Mutation Taster		=92/8	polymorphism

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

hg19: chr1-45977043;