Variant chr2-149587299-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015702.3(MMADHC):c.-52-150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 619,970 control chromosomes in the GnomAD database, including 224,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 44451 hom., cov: 31)

Exomes 𝑓: 0.87 ( 179811 hom. )

Consequence

MMADHC
NM_015702.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.85

Variant links:

Genes affected

MMADHC (HGNC:25221): (metabolism of cobalamin associated D) This gene encodes a mitochondrial protein that is involved in an early step of vitamin B12 metabolism. Vitamin B12 (cobalamin) is essential for normal development and survival in humans. Mutations in this gene cause methylmalonic aciduria and homocystinuria type cblD (MMADHC), a disorder of cobalamin metabolism that is characterized by decreased levels of the coenzymes adenosylcobalamin and methylcobalamin. Pseudogenes have been identified on chromosomes 11 and X.[provided by RefSeq, Nov 2008]

MMADHC links:

MMADHC-DT (HGNC:41087): (MMADHC divergent transcript)

MMADHC-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 2-149587299-C-T is Benign according to our data. Variant chr2-149587299-C-T is described in ClinVar as [Benign]. Clinvar id is 1247490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMADHC	NM_015702.3 linkuse as main transcript	c.-52-150G>A		intron_variant		ENST00000303319.10	NP_056517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMADHC	ENST00000303319.10 linkuse as main transcript	c.-52-150G>A		intron_variant		1	NM_015702.3	ENSP00000301920	P1

Frequencies

GnomAD3 genomes

AF:

0.721

AC:

109492

AN:

151932

Hom.:

44446

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.889

Gnomad AMR

AF:

0.718

Gnomad ASJ

AF:

0.882

Gnomad EAS

AF:

0.863

Gnomad SAS

AF:

0.897

Gnomad FIN

AF:

0.942

Gnomad MID

AF:

0.820

Gnomad NFE

AF:

0.896

Gnomad OTH

AF:

0.754

GnomAD4 exome

AF:

0.870

AC:

407109

AN:

467920

Hom.:

179811

Cov.:

AF XY:

0.875

AC XY:

218041

AN XY:

249246

show subpopulations

Gnomad4 AFR exome

AF:

0.321

Gnomad4 AMR exome

AF:

0.736

Gnomad4 ASJ exome

AF:

0.886

Gnomad4 EAS exome

AF:

0.877

Gnomad4 SAS exome

AF:

0.900

Gnomad4 FIN exome

AF:

0.935

Gnomad4 NFE exome

AF:

0.895

Gnomad4 OTH exome

AF:

0.840

GnomAD4 genome

AF:

0.720

AC:

109511

AN:

152050

Hom.:

44451

Cov.:

AF XY:

0.726

AC XY:

53958

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.718

Gnomad4 ASJ

AF:

0.882

Gnomad4 EAS

AF:

0.863

Gnomad4 SAS

AF:

0.898

Gnomad4 FIN

AF:

0.942

Gnomad4 NFE

AF:

0.896

Gnomad4 OTH

AF:

0.755

Alfa

AF:

0.855

Hom.:

40243

Bravo

AF:

0.684

Asia WGS

AF:

0.846

AC:

2939

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.9

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over