Variant chr6-49444562-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000255.4(MMUT):c.1676+77A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,178,926 control chromosomes in the GnomAD database, including 35,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3841 hom., cov: 32)

Exomes 𝑓: 0.24 ( 31588 hom. )

Consequence

MMUT
NM_000255.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.539

Variant links:

Genes affected

MMUT (HGNC:7526): (methylmalonyl-CoA mutase) This gene encodes the mitochondrial enzyme methylmalonyl Coenzyme A mutase. In humans, the product of this gene is a vitamin B12-dependent enzyme which catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA, while in other species this enzyme may have different functions. Mutations in this gene may lead to various types of methylmalonic aciduria. [provided by RefSeq, Jul 2008]

MMUT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 6-49444562-T-G is Benign according to our data. Variant chr6-49444562-T-G is described in ClinVar as [Benign]. Clinvar id is 498783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-49444562-T-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMUT	NM_000255.4 linkuse as main transcript	c.1676+77A>C		intron_variant		ENST00000274813.4	NP_000246.2
MMUT	XM_005249143.4 linkuse as main transcript	c.1676+77A>C		intron_variant			XP_005249200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMUT	ENST00000274813.4 linkuse as main transcript	c.1676+77A>C		intron_variant		1	NM_000255.4	ENSP00000274813	P1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33392

AN:

151956

Hom.:

3838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.279

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.220

GnomAD4 exome

AF:

0.244

AC:

250114

AN:

1026852

Hom.:

31588

AF XY:

0.247

AC XY:

131215

AN XY:

530514

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.189

Gnomad4 EAS exome

AF:

0.207

Gnomad4 SAS exome

AF:

0.284

Gnomad4 FIN exome

AF:

0.229

Gnomad4 NFE exome

AF:

0.254

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.220

AC:

33408

AN:

152074

Hom.:

3841

Cov.:

AF XY:

0.219

AC XY:

16242

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.174

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.241

Gnomad4 SAS

AF:

0.277

Gnomad4 FIN

AF:

0.230

Gnomad4 NFE

AF:

0.256

Gnomad4 OTH

AF:

0.218

Alfa

AF:

0.244

Hom.:

2231

Bravo

AF:

0.211

Asia WGS

AF:

0.204

AC:

708

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 27884173, 21671183) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 06, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 19, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 06, 2017

- -

Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Aug 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.7

DANN

Benign

0.80

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