rs9473555

chr6-49441774-G-Cchr6-49441774-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000255.4(MMUT):c.1808+66C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,514,896 control chromosomes in the GnomAD database, including 99,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9680 hom., cov: 31)
  • Exomes 𝑓: 0.36 (89875 hom.)
• Consequence: MMUT NM_000255.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.462

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-49441774-G-C is Benign according to our data. Variant chr6-49441774-G-C is described in ClinVar as [Benign]. Clinvar id is 1248555.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.1808+66C>G		intron_variant		ENST00000274813.4
MMUT	XM_005249143.4	c.1808+66C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMUT	ENST00000274813.4	c.1808+66C>G		intron_variant		1	NM_000255.4	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53465 AN: 150658 Hom.: 9667 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.359 AC: 490399 AN: 1364142 Hom.: 89875 AF XY: 0.359 AC XY: 242897 AN XY: 677342

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.355 AC: 53507 AN: 150754 Hom.: 9680 Cov.: 31 AF XY: 0.351 AC XY: 25875 AN XY: 73638

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.327

Alfa AF: 0.242 Hom.: 594

Bravo AF: 0.343

Asia WGS AF: 0.339 AC: 1182 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	10
Dann	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9473555; hg19: chr6-49409487; COSMIC: COSV51272685;