Variant rs6458690 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000255.4(MMUT):c.1676+733T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 342,034 control chromosomes in the GnomAD database, including 22,848 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 0.36 ( 10225 hom., cov: 31)

Exomes 𝑓: 0.37 ( 12623 hom. )

Consequence

MMUT
NM_000255.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.771

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 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+733T>C		intron_variant		ENST00000274813.4	NP_000246.2
MMUT	XM_005249143.4 linkuse as main transcript	c.1676+733T>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+733T>C		intron_variant		1	NM_000255.4	ENSP00000274813	P1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55111

AN:

151774

Hom.:

10211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.260

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.333

GnomAD4 exome

AF:

0.369

AC:

70189

AN:

190142

Hom.:

12623

AF XY:

0.370

AC XY:

41607

AN XY:

112466

show subpopulations

Gnomad4 AFR exome

AF:

0.444

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.356

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.369

Gnomad4 FIN exome

AF:

0.391

Gnomad4 NFE exome

AF:

0.388

Gnomad4 OTH exome

AF:

0.375

GnomAD4 genome

AF:

0.363

AC:

55158

AN:

151892

Hom.:

10225

Cov.:

AF XY:

0.360

AC XY:

26688

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.411

Gnomad4 AMR

AF:

0.260

Gnomad4 ASJ

AF:

0.350

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.372

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.334

Alfa

AF:

0.366

Hom.:

4765

Bravo

AF:

0.352

Asia WGS

AF:

0.342

AC:

1193

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.6

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over