4-145619459-C-T

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.-66+52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,320 control chromosomes in the GnomAD database, including 554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.075 (553 hom., cov: 32)
  • Exomes 𝑓: 0.073 (1 hom.)
• Consequence: MMAA NM_172250.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0120

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=-0.71).
• BP6: Variant 4-145619459-C-T is Benign according to our data. Variant chr4-145619459-C-T is described in ClinVar as [Benign]. Clinvar id is 1240548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMAA	NM_172250.3	c.-66+52C>T		intron_variant		ENST00000649156.2
MMAA	NM_001375644.1	c.-256C>T		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMAA	ENST00000649156.2	c.-66+52C>T		intron_variant			NM_172250.3	P1

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11429 AN: 152092 Hom.: 555 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0524

Gnomad OTH AF: 0.0536

GnomAD4 exome AF: 0.0727 AC: 8 AN: 110 Hom.: 1 AF XY: 0.0854 AC XY: 7 AN XY: 82

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0510

GnomAD4 genome AF: 0.0751 AC: 11436 AN: 152210 Hom.: 553 Cov.: 32 AF XY: 0.0758 AC XY: 5641 AN XY: 74428

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0600

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.0883

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0545

Gnomad4 NFE AF: 0.0524

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0650 Hom.: 57

Bravo AF: 0.0739

Asia WGS AF: 0.110 AC: 383 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

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	3.7
Dann	Benign	0.96

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: rs114699496; hg19: chr4-146540611;