19-8302475-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_016579.4(CD320):c.837C>G(p.Thr279Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 1,614,016 control chromosomes in the GnomAD database, including 4,830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 2032 hom., cov: 32)

Exomes 𝑓: 0.044 ( 2798 hom. )

Consequence

CD320
NM_016579.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.137

Publications

15 publications found

Variant links:

Genes affected

CD320 (HGNC:16692): (CD320 molecule) This gene encodes the transcobalamin receptor that is expressed at the cell surface. It mediates the cellular uptake of transcobalamin bound cobalamin (vitamin B12), and is involved in B-cell proliferation and immunoglobulin secretion. Mutations in this gene are associated with methylmalonic aciduria. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

CD320 Gene-Disease associations (from GenCC):

methylmalonic acidemia due to transcobalamin receptor defect
Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen, Laboratory for Molecular Medicine

CD320 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.053).

BP6

Variant 19-8302475-G-C is Benign according to our data. Variant chr19-8302475-G-C is described in ClinVar as Benign. ClinVar VariationId is 136686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.137 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016579.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD320	NM_016579.4	MANE Select	c.837C>G	p.Thr279Thr	synonymous	Exon 5 of 5	NP_057663.1
	CD320	NM_001165895.2		c.711C>G	p.Thr237Thr	synonymous	Exon 4 of 4	NP_001159367.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD320	ENST00000301458.10	TSL:1 MANE Select	c.837C>G	p.Thr279Thr	synonymous	Exon 5 of 5	ENSP00000301458.4
CD320	ENST00000596002.5	TSL:1	n.*1125C>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000471773.1
CD320	ENST00000596002.5	TSL:1	n.*1125C>G		3_prime_UTR	Exon 5 of 5	ENSP00000471773.1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17380

AN:

152098

Hom.:

2024

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0685

Gnomad ASJ

AF:

0.0579

Gnomad EAS

AF:

0.0884

Gnomad SAS

AF:

0.0393

Gnomad FIN

AF:

0.0298

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0348

Gnomad OTH

AF:

0.103

GnomAD2 exomes

AF:

0.0590

AC:

14826

AN:

251384

AF XY:

0.0534

show subpopulations

Gnomad AFR exome

AF:

0.312

Gnomad AMR exome

AF:

0.0455

Gnomad ASJ exome

AF:

0.0634

Gnomad EAS exome

AF:

0.0883

Gnomad FIN exome

AF:

0.0272

Gnomad NFE exome

AF:

0.0346

Gnomad OTH exome

AF:

0.0487

GnomAD4 exome

AF:

0.0437

AC:

63862

AN:

1461800

Hom.:

2798

Cov.:

AF XY:

0.0425

AC XY:

30870

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.312

AC:

10436

AN:

33472

American (AMR)

AF:

0.0479

AC:

2144

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0611

AC:

1596

AN:

26136

East Asian (EAS)

AF:

0.0728

AC:

2890

AN:

39700

South Asian (SAS)

AF:

0.0346

AC:

2981

AN:

86256

European-Finnish (FIN)

AF:

0.0282

AC:

1506

AN:

53372

Middle Eastern (MID)

AF:

0.0666

AC:

384

AN:

5768

European-Non Finnish (NFE)

AF:

0.0345

AC:

38338

AN:

1111980

Other (OTH)

AF:

0.0594

AC:

3587

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

3440

6880

10321

13761

17201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1676

3352

5028

6704

8380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.114

AC:

17410

AN:

152216

Hom.:

2032

Cov.:

AF XY:

0.113

AC XY:

8427

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.303

AC:

12578

AN:

41482

American (AMR)

AF:

0.0685

AC:

1047

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0579

AC:

201

AN:

3470

East Asian (EAS)

AF:

0.0886

AC:

459

AN:

5180

South Asian (SAS)

AF:

0.0391

AC:

189

AN:

4828

European-Finnish (FIN)

AF:

0.0298

AC:

316

AN:

10620

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0348

AC:

2365

AN:

68022

Other (OTH)

AF:

0.101

AC:

214

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

692

1384

2075

2767

3459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0348

Hom.:

Bravo

AF:

0.127

Asia WGS

AF:

0.0810

AC:

283

AN:

3478

EpiCase

AF:

0.0425

EpiControl

AF:

0.0385

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 26, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Methylmalonic acidemia due to transcobalamin receptor defect

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.65

(source)

DANN

Benign

0.39

PhyloP100

0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over