Variant 1-45511583-CAT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.837

Variant links:

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]

MMACHC links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MMACHC	NM_015506.3 linkuse as main transcript	c.2372_2373delTA		3_prime_UTR_variant	4/4	ENST00000401061.9	NP_056321.2	Q9Y4U1
PRDX1	NM_181697.3 linkuse as main transcript	c.515-171_515-170delAT		intron_variant		ENST00000319248.13	NP_859048.1	Q06830A0A384NPQ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMACHC	ENST00000401061.9 linkuse as main transcript	c.2372_2373delTA		3_prime_UTR_variant	4/4	2	NM_015506.3	ENSP00000383840.4		Q9Y4U1
PRDX1	ENST00000319248.13 linkuse as main transcript	c.515-171_515-170delAT		intron_variant		1	NM_181697.3	ENSP00000361152.5		Q06830

Frequencies

GnomAD3 genomes

AF:

0.0645

AC:

9798

AN:

151994

Hom.:

1023

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.217

Gnomad4 AMR exome

AF:

0.0179

Gnomad4 ASJ exome

AF:

0.0264

Gnomad4 EAS exome

AF:

0.00831

Gnomad4 SAS exome

AF:

0.00302

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00103

Gnomad4 OTH exome

AF:

0.0253

GnomAD4 genome

AF:

0.0645

AC:

9814

AN:

152112

Hom.:

1023

Cov.:

AF XY:

0.0633

AC XY:

4709

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.0253

Gnomad4 ASJ

AF:

0.0231

Gnomad4 EAS

AF:

0.0131

Gnomad4 SAS

AF:

0.00538

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.0455

Alfa

AF:

0.0466

Hom.:

Bravo

AF:

0.0734

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over