NM_016579.4:c.23A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016579.4(CD320):c.23A>G(p.Gln8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 1,582,434 control chromosomes in the GnomAD database, including 9,897 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 3924 hom., cov: 33)

Exomes 𝑓: 0.056 ( 5973 hom. )

Consequence

CD320
NM_016579.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0190

Publications

21 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:

ENSG00000167774 (HGNC:):

ENSG00000167774 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.4540892E-4).

BP6

Variant 19-8308268-T-C is Benign according to our data. Variant chr19-8308268-T-C is described in ClinVar as Benign. ClinVar VariationId is 136683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD320	NM_016579.4 link	c.23A>G	p.Gln8Arg	missense_variant	Exon 1 of 5	ENST00000301458.10	NP_057663.1	Q9NPF0-1
CD320	NM_001165895.2 link	c.23A>G	p.Gln8Arg	missense_variant	Exon 1 of 4		NP_001159367.1	Q9NPF0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD320	ENST00000301458.10 link	c.23A>G	p.Gln8Arg	missense_variant	Exon 1 of 5	1	NM_016579.4	ENSP00000301458.4		Q9NPF0-1
ENSG00000167774	ENST00000598884.1 link	n.*232A>G		downstream_gene_variant		4		ENSP00000470609.1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23211

AN:

152044

Hom.:

3903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0785

Gnomad ASJ

AF:

0.0580

Gnomad EAS

AF:

0.0893

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.0297

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0353

Gnomad OTH

AF:

0.126

GnomAD2 exomes

AF:

0.0825

AC:

16026

AN:

194160

AF XY:

0.0843

show subpopulations

Gnomad AFR exome

AF:

0.403

Gnomad AMR exome

AF:

0.0478

Gnomad ASJ exome

AF:

0.0626

Gnomad EAS exome

AF:

0.0854

Gnomad FIN exome

AF:

0.0255

Gnomad NFE exome

AF:

0.0331

Gnomad OTH exome

AF:

0.0578

GnomAD4 exome

AF:

0.0563

AC:

80467

AN:

1430272

Hom.:

5973

Cov.:

AF XY:

0.0589

AC XY:

41862

AN XY:

710656

show subpopulations

African (AFR)

AF:

0.431

AC:

14155

AN:

32854

American (AMR)

AF:

0.0516

AC:

2223

AN:

43084

Ashkenazi Jewish (ASJ)

AF:

0.0607

AC:

1559

AN:

25686

East Asian (EAS)

AF:

0.0719

AC:

2785

AN:

38722

South Asian (SAS)

AF:

0.186

AC:

15577

AN:

83854

European-Finnish (FIN)

AF:

0.0275

AC:

1057

AN:

38490

Middle Eastern (MID)

AF:

0.0801

AC:

457

AN:

5704

European-Non Finnish (NFE)

AF:

0.0346

AC:

38150

AN:

1102438

Other (OTH)

AF:

0.0758

AC:

4504

AN:

59440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

3749

7498

11248

14997

18746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1814

3628

5442

7256

9070

<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:

0.153

AC:

23274

AN:

152162

Hom.:

3924

Cov.:

AF XY:

0.154

AC XY:

11428

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.419

AC:

17358

AN:

41460

American (AMR)

AF:

0.0784

AC:

1198

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0580

AC:

201

AN:

3466

East Asian (EAS)

AF:

0.0895

AC:

462

AN:

5162

South Asian (SAS)

AF:

0.214

AC:

1035

AN:

4830

European-Finnish (FIN)

AF:

0.0297

AC:

315

AN:

10614

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0353

AC:

2401

AN:

68022

Other (OTH)

AF:

0.123

AC:

261

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

822

1644

2467

3289

4111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.0604

Hom.:

1338

Bravo

AF:

0.165

TwinsUK

AF:

0.0378

AC:

140

ALSPAC

AF:

0.0368

AC:

142

ESP6500AA

AF:

0.309

AC:

1254

ESP6500EA

AF:

0.0315

AC:

261

ExAC

AF:

0.0787

AC:

9235

Asia WGS

AF:

0.166

AC:

577

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 03, 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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

1.0

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.031

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.18

T;T

MetaRNN

Benign

0.00035

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

N;N

PhyloP100

-0.019

PrimateAI

Benign

0.45

PROVEAN

Benign

1.2

N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.029

MPC

0.12

ClinPred

0.0026

GERP RS

1.9

PromoterAI

-0.054

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.034

gMVP

0.75

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over