dbSNP rs2232775: CD320:p.Gln8Leu (chr19-8308268-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016579.4(CD320):c.23A>T(p.Gln8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000629 in 1,430,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q8R) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

CD320
NM_016579.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0190

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.071531355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD320	NM_016579.4 link	c.23A>T	p.Gln8Leu	missense_variant	Exon 1 of 5	ENST00000301458.10	NP_057663.1	Q9NPF0-1
CD320	NM_001165895.2 link	c.23A>T	p.Gln8Leu	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>T	p.Gln8Leu	missense_variant	Exon 1 of 5	1	NM_016579.4	ENSP00000301458.4		Q9NPF0-1
ENSG00000167774	ENST00000598884.1 link	n.*232A>T		downstream_gene_variant		4		ENSP00000470609.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000629

AC:

AN:

1430526

Hom.:

Cov.:

AF XY:

0.00000563

AC XY:

AN XY:

710806

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32906

American (AMR)

AF:

0.00

AC:

AN:

43104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25688

East Asian (EAS)

AF:

0.00

AC:

AN:

38744

South Asian (SAS)

AF:

0.00

AC:

AN:

83908

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00000816

AC:

AN:

1102512

Other (OTH)

AF:

0.00

AC:

AN:

59448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Benign

5.5

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.078

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.21

T;T

M_CAP

Benign

0.079

MetaRNN

Benign

0.072

T;T

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

0.0

N;N

PhyloP100

-0.019

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

0.0

.;B

Vest4

0.11

MutPred

0.36

Loss of disorder (P = 0.0566);Loss of disorder (P = 0.0566);

MVP

0.74

MPC

0.11

ClinPred

0.12

GERP RS

1.9

PromoterAI

0.063

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.097

gMVP

0.84

Mutation Taster

=99/1

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over