chr2-219210394-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005689.4(ABCB6):​c.2338G>T​(p.Val780Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V780I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ABCB6
NM_005689.4 missense

Scores

1
10
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.19
Variant links:
Genes affected
ABCB6 (HGNC:47): (ATP binding cassette subfamily B member 6 (LAN blood group)) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ABC proteins transport various molecules across extra- and intra-cellular membranes. This protein is a member of the heavy metal importer subfamily and plays a role in porphyrin transport. This gene is the molecular basis of the Langereis (Lan) blood group antigen and mutations in this gene underlie familial pseudohyperkalemia and dyschromatosis universalis hereditaria. [provided by RefSeq, Mar 2017]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCB6NM_005689.4 linkc.2338G>T p.Val780Leu missense_variant Exon 17 of 19 ENST00000265316.9 NP_005680.1 Q9NP58-1
ABCB6NM_001349828.2 linkc.2200G>T p.Val734Leu missense_variant Exon 16 of 18 NP_001336757.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCB6ENST00000265316.9 linkc.2338G>T p.Val780Leu missense_variant Exon 17 of 19 1 NM_005689.4 ENSP00000265316.3 Q9NP58-1
ENSG00000284820ENST00000446716.5 linkn.*4122G>T non_coding_transcript_exon_variant Exon 20 of 22 2 ENSP00000398528.1 H7C152
ENSG00000284820ENST00000446716.5 linkn.*4122G>T 3_prime_UTR_variant Exon 20 of 22 2 ENSP00000398528.1 H7C152

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Uncertain
0.063
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T;.
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.16
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
0.97
D;D
M_CAP
Uncertain
0.095
D
MetaRNN
Uncertain
0.55
D;D
MetaSVM
Uncertain
0.047
D
MutationAssessor
Benign
0.41
N;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-2.1
N;.
REVEL
Uncertain
0.51
Sift
Uncertain
0.011
D;.
Sift4G
Uncertain
0.019
D;.
Polyphen
0.97
D;D
Vest4
0.69
MutPred
0.47
Loss of catalytic residue at V780 (P = 0.0763);.;
MVP
0.98
MPC
0.33
ClinPred
0.81
D
GERP RS
2.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.49
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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.

Other links and lift over

dbSNP: rs201104967; hg19: chr2-220075116; API