Variant 2-149575863-C-G 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.479-22G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,553,354 control chromosomes in the GnomAD database, including 458,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 35624 hom., cov: 33)

Exomes 𝑓: 0.77 ( 422844 hom. )

Consequence

MMADHC
NM_015702.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.14

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-149575863-C-G is Benign according to our data. Variant chr2-149575863-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 260678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMADHC	NM_015702.3 linkuse as main transcript	c.479-22G>C		intron_variant		ENST00000303319.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
MMADHC	ENST00000303319.10 linkuse as main transcript	c.479-22G>C	intron_variant	1	NM_015702.3	P1
MMADHC	ENST00000422782.2 linkuse as main transcript	c.479-22G>C	intron_variant	5
MMADHC	ENST00000428879.5 linkuse as main transcript	c.479-22G>C	intron_variant	2		P1

Frequencies

GnomAD3 genomes

AF:

0.649

AC:

98502

AN:

151850

Hom.:

35618

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.754

Gnomad AMR

AF:

0.658

Gnomad ASJ

AF:

0.801

Gnomad EAS

AF:

0.859

Gnomad SAS

AF:

0.766

Gnomad FIN

AF:

0.850

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.791

Gnomad OTH

AF:

0.672

GnomAD3 exomes

AF:

0.751

AC:

168708

AN:

224514

Hom.:

65139

AF XY:

0.759

AC XY:

92148

AN XY:

121354

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.706

Gnomad ASJ exome

AF:

0.811

Gnomad EAS exome

AF:

0.858

Gnomad SAS exome

AF:

0.759

Gnomad FIN exome

AF:

0.850

Gnomad NFE exome

AF:

0.783

Gnomad OTH exome

AF:

0.757

GnomAD4 exome

AF:

0.772

AC:

1081754

AN:

1401388

Hom.:

422844

Cov.:

AF XY:

0.773

AC XY:

539225

AN XY:

697548

show subpopulations

Gnomad4 AFR exome

AF:

0.278

Gnomad4 AMR exome

AF:

0.697

Gnomad4 ASJ exome

AF:

0.801

Gnomad4 EAS exome

AF:

0.873

Gnomad4 SAS exome

AF:

0.760

Gnomad4 FIN exome

AF:

0.847

Gnomad4 NFE exome

AF:

0.784

Gnomad4 OTH exome

AF:

0.756

GnomAD4 genome

AF:

0.648

AC:

98521

AN:

151966

Hom.:

35624

Cov.:

AF XY:

0.653

AC XY:

48479

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.302

Gnomad4 AMR

AF:

0.658

Gnomad4 ASJ

AF:

0.801

Gnomad4 EAS

AF:

0.859

Gnomad4 SAS

AF:

0.767

Gnomad4 FIN

AF:

0.850

Gnomad4 NFE

AF:

0.791

Gnomad4 OTH

AF:

0.673

Alfa

AF:

0.709

Hom.:

5319

Bravo

AF:

0.618

Asia WGS

AF:

0.789

AC:

2711

AN:

3438

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Methylmalonic aciduria and homocystinuria type cblD

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

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

-0.83

Cadd

Benign

0.85

Dann

Benign

0.66

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

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