6-49430620-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000255.4(MMUT):c.*1107_*1108insA 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 0.35 (9729 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: MMUT NM_000255.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0350

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 -10 ACMG points.

• BP6: Variant 6-49430620-G-GT is Benign according to our data. Variant chr6-49430620-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 357238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMUT	NM_000255.4	c.*1107_*1108insA		3_prime_UTR_variant	13/13	ENST00000274813.4
MMUT	XM_005249143.4	c.*1107_*1108insA		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMUT	ENST00000274813.4	c.*1107_*1108insA		3_prime_UTR_variant	13/13	1	NM_000255.4	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53832 AN: 151788 Hom.: 9715 Cov.: 0

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.326

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.355 AC: 53883 AN: 151906 Hom.: 9729 Cov.: 0 AF XY: 0.351 AC XY: 26099 AN XY: 74258

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.327

Alfa AF: 0.360 Hom.: 1257

Bravo AF: 0.342

Asia WGS AF: 0.341 AC: 1186 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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: rs71777574; hg19: chr6-49398333;