6-49431526-AT-A

Position:

• chr6-49431526-AT-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000255.4(MMUT):​c.*201del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (9856 hom., cov: 0)
  • Exomes 𝑓: 0.35 (17834 hom.)
• Consequence: MMUT NM_000255.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0410

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 6-49431526-AT-A is Benign according to our data. Variant chr6-49431526-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 357247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMUT	NM_000255.4	c.*201del		3_prime_UTR_variant	13/13	ENST00000274813.4	NP_000246.2
MMUT	XM_005249143.4	c.*201del		3_prime_UTR_variant	13/13		XP_005249200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMUT	ENST00000274813.4	c.*201del		3_prime_UTR_variant	13/13	1	NM_000255.4	ENSP00000274813	P1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54062 AN: 150418 Hom.: 9843 Cov.: 0

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.221

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.352 AC: 107252 AN: 304382 Hom.: 17834 Cov.: 0 AF XY: 0.353 AC XY: 57090 AN XY: 161898

Gnomad4 AFR exome AF: 0.397

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.359

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.359 AC: 54108 AN: 150528 Hom.: 9856 Cov.: 0 AF XY: 0.356 AC XY: 26161 AN XY: 73450

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.333

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Methylmalonic acidemia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs10713340; hg19: chr6-49399239;