rs71777574

Variant names:

• chr6-49430620-G-GT
• rs71777574
• NM_000255.4:c.*1107dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000255.4(MMUT):​c.*1107dupA 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
• Publications: 0 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 -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 rank	MANE	Protein	UniProt
MMUT	NM_000255.4	c.*1107dupA		3_prime_UTR_variant	Exon 13 of 13	ENST00000274813.4	NP_000246.2
MMUT	XM_005249143.4	c.*1107dupA		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.*1107dupA		3_prime_UTR_variant	Exon 13 of 13	1	NM_000255.4	ENSP00000274813.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.385 AC: 15945 AN: 41400

American (AMR) AF: 0.255 AC: 3891 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1209 AN: 3468

East Asian (EAS) AF: 0.219 AC: 1130 AN: 5160

South Asian (SAS) AF: 0.371 AC: 1788 AN: 4816

European-Finnish (FIN) AF: 0.372 AC: 3925 AN: 10550

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.367 AC: 24953 AN: 67938

Other (OTH) AF: 0.327 AC: 689 AN: 2108

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.035
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: rs71777574; hg19: chr6-49398333;