4-145638826-A-C

Variant summary

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

The NM_172250.3(MMAA):c.-65-249A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 152,254 control chromosomes in the GnomAD database, including 380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.064 (380 hom., cov: 32)
• Consequence: MMAA NM_172250.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17

Genes affected

MMAA (HGNC:18871): (metabolism of cobalamin associated A) The protein encoded by this gene is involved in the translocation of cobalamin into the mitochondrion, where it is used in the final steps of adenosylcobalamin synthesis. Adenosylcobalamin is a coenzyme required for the activity of methylmalonyl-CoA mutase. Defects in this gene are a cause 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=-0.82).
• BP6: Variant 4-145638826-A-C is Benign according to our data. Variant chr4-145638826-A-C is described in ClinVar as [Benign]. Clinvar id is 1226045.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMAA	NM_172250.3	c.-65-249A>C		intron_variant		ENST00000649156.2
MMAA	NM_001375644.1	c.-65-249A>C		intron_variant
MMAA	XM_011531684.4	c.-65-249A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMAA	ENST00000649156.2	c.-65-249A>C		intron_variant			NM_172250.3	P1

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9745 AN: 152136 Hom.: 380 Cov.: 32

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0739

Gnomad OTH AF: 0.0793

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0641 AC: 9753 AN: 152254 Hom.: 380 Cov.: 32 AF XY: 0.0621 AC XY: 4620 AN XY: 74450

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.0489

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0831

Gnomad4 FIN AF: 0.0465

Gnomad4 NFE AF: 0.0739

Gnomad4 OTH AF: 0.0779

Alfa AF: 0.0670 Hom.: 40

Bravo AF: 0.0648

Asia WGS AF: 0.0330 AC: 116 AN: 3478

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

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	13
Dann	Benign	0.72

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: rs80026420; hg19: chr4-146559978;