1-45511583-CAT-C

Variant names:

• chr1-45511583-CAT-C
• rs10610450
• NM_015506.3:c.*2372_*2373delTA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015506.3(MMACHC):​c.*2372_*2373delTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 444,644 control chromosomes in the GnomAD database, including 1,256 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.065 (1023 hom., cov: 31)
  • Exomes 𝑓: 0.011 (233 hom.)
• Consequence: MMACHC NM_015506.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.837
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 1-45511583-CAT-C is Benign according to our data. Variant chr1-45511583-CAT-C is described in ClinVar as [Benign]. Clinvar id is 1251776.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMACHC	NM_015506.3	c.*2372_*2373delTA		3_prime_UTR_variant	Exon 4 of 4	ENST00000401061.9	NP_056321.2
PRDX1	NM_181697.3	c.515-171_515-170delAT		intron_variant	Intron 5 of 5	ENST00000319248.13	NP_859048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMACHC	ENST00000401061.9	c.*2372_*2373delTA		3_prime_UTR_variant	Exon 4 of 4	2	NM_015506.3	ENSP00000383840.4
PRDX1	ENST00000319248.13	c.515-171_515-170delAT		intron_variant	Intron 5 of 5	1	NM_181697.3	ENSP00000361152.5

Frequencies

GnomAD3 genomes AF: 0.0645 AC: 9798 AN: 151994 Hom.: 1023 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0254

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.0455

GnomAD4 exome AF: 0.0108 AC: 3154 AN: 292532 Hom.: 233 AF XY: 0.00899 AC XY: 1374 AN XY: 152788

African (AFR) AF: 0.217 AC: 1770 AN: 8140

American (AMR) AF: 0.0179 AC: 160 AN: 8928

Ashkenazi Jewish (ASJ) AF: 0.0264 AC: 263 AN: 9978

East Asian (EAS) AF: 0.00831 AC: 201 AN: 24194

South Asian (SAS) AF: 0.00302 AC: 39 AN: 12930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25042

Middle Eastern (MID) AF: 0.0233 AC: 70 AN: 3008

European-Non Finnish (NFE) AF: 0.00103 AC: 188 AN: 182022

Other (OTH) AF: 0.0253 AC: 463 AN: 18290

GnomAD4 genome AF: 0.0645 AC: 9814 AN: 152112 Hom.: 1023 Cov.: 31 AF XY: 0.0633 AC XY: 4709 AN XY: 74402

African (AFR) AF: 0.219 AC: 9066 AN: 41442

American (AMR) AF: 0.0253 AC: 387 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3464

East Asian (EAS) AF: 0.0131 AC: 68 AN: 5184

South Asian (SAS) AF: 0.00538 AC: 26 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00113 AC: 77 AN: 68014

Other (OTH) AF: 0.0455 AC: 96 AN: 2108

Alfa AF: 0.0466 Hom.: 63

Bravo AF: 0.0734

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 22, 2021

GeneDx

Significance: 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
PhyloP100		0.84
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: rs10610450; hg19: chr1-45977255;