6-49431526-AT-A

Variant names:

• chr6-49431526-AT-A
• rs10713340
• NM_000255.4:c.*201delA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000255.4(MMUT):​c.*201delA 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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• vitamin B12-unresponsive methylmalonic acidemia type mut-

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• vitamin B12-unresponsive methylmalonic acidemia type mut0

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MMUT	NM_000255.4	c.*201delA		3_prime_UTR_variant	Exon 13 of 13	ENST00000274813.4	NP_000246.2
MMUT	XM_005249143.4	c.*201delA		3_prime_UTR_variant	Exon 13 of 13		XP_005249200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMUT	ENST00000274813.4	c.*201delA		3_prime_UTR_variant	Exon 13 of 13	1	NM_000255.4	ENSP00000274813.3

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

African (AFR) AF: 0.397 AC: 3487 AN: 8792

American (AMR) AF: 0.243 AC: 2899 AN: 11922

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 3112 AN: 8762

East Asian (EAS) AF: 0.239 AC: 4560 AN: 19074

South Asian (SAS) AF: 0.359 AC: 12038 AN: 33494

European-Finnish (FIN) AF: 0.374 AC: 8478 AN: 22698

Middle Eastern (MID) AF: 0.279 AC: 353 AN: 1266

European-Non Finnish (NFE) AF: 0.366 AC: 66504 AN: 181772

Other (OTH) AF: 0.351 AC: 5821 AN: 16602

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

African (AFR) AF: 0.393 AC: 16151 AN: 41106

American (AMR) AF: 0.260 AC: 3913 AN: 15054

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1306 AN: 3464

East Asian (EAS) AF: 0.220 AC: 1121 AN: 5104

South Asian (SAS) AF: 0.374 AC: 1776 AN: 4744

European-Finnish (FIN) AF: 0.379 AC: 3878 AN: 10242

Middle Eastern (MID) AF: 0.224 AC: 65 AN: 290

European-Non Finnish (NFE) AF: 0.369 AC: 24914 AN: 67534

Other (OTH) AF: 0.333 AC: 693 AN: 2084

Alfa AF: 0.185 Hom.: 346

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Aug 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Methylmalonic acidemia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.041
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10713340; hg19: chr6-49399239; COSMIC: COSV51272233;