Variant 2-149569810-T-C 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.*164A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 652,832 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 61 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 75 hom. )

Consequence

MMADHC
NM_015702.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00100

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:

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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=-0.83).

BP6

Variant 2-149569810-T-C is Benign according to our data. Variant chr2-149569810-T-C is described in ClinVar as [Benign]. Clinvar id is 331372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0725 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.*164A>G		3_prime_UTR_variant	8/8	ENST00000303319.10	NP_056517.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
MMADHC	ENST00000303319.10 linkuse as main transcript	c.*164A>G	3_prime_UTR_variant	8/8	1	NM_015702.3	ENSP00000301920	P1
MMADHC	ENST00000422782.2 linkuse as main transcript	c.*164A>G	3_prime_UTR_variant	9/9	5		ENSP00000408331
MMADHC	ENST00000428879.5 linkuse as main transcript	c.*164A>G	3_prime_UTR_variant	7/7	2		ENSP00000389060	P1

Frequencies

GnomAD3 genomes

AF:

0.00969

AC:

1474

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0764

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.0115

GnomAD4 exome

AF:

0.00481

AC:

2408

AN:

500532

Hom.:

Cov.:

AF XY:

0.00445

AC XY:

1171

AN XY:

263190

show subpopulations

Gnomad4 AFR exome

AF:

0.00543

Gnomad4 AMR exome

AF:

0.0742

Gnomad4 ASJ exome

AF:

0.000548

Gnomad4 EAS exome

AF:

0.0000650

Gnomad4 SAS exome

AF:

0.00288

Gnomad4 FIN exome

AF:

0.0000307

Gnomad4 NFE exome

AF:

0.00124

Gnomad4 OTH exome

AF:

0.00692

GnomAD4 genome

AF:

0.00967

AC:

1472

AN:

152300

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

819

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00433

Gnomad4 AMR

AF:

0.0761

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00428

Hom.:

Bravo

AF:

0.0148

Asia WGS

AF:

0.00491

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Disorders of Intracellular Cobalamin Metabolism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Methylmalonic aciduria and homocystinuria type cblD

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.0

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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