rs1141321

Variant names:

• chr6-49444720-C-A
• NM_000255.4:c.1595G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-49444720-C-A
• chr6-49444720-C-G
• chr6-49444720-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000255.4(MMUT):​c.1595G>T​(p.Arg532Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R532H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MMUT NM_000255.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21435067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMUT	NM_000255.4	c.1595G>T	p.Arg532Leu	missense_variant	Exon 9 of 13	ENST00000274813.4	NP_000246.2
MMUT	XM_005249143.4	c.1595G>T	p.Arg532Leu	missense_variant	Exon 9 of 13		XP_005249200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMUT	ENST00000274813.4	c.1595G>T	p.Arg532Leu	missense_variant	Exon 9 of 13	1	NM_000255.4	ENSP00000274813.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461140 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726876

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.069	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	14
DANN	Benign	0.97
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	0.26	D
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.36
Sift	Benign	0.10	T
Sift4G	Benign	0.11	T
Vest4		0.32
MutPred		0.54		Loss of solvent accessibility (P = 0.0299);
MVP		0.79
MPC		0.12
ClinPred		0.23	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-49412433;