Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The ENST00000265316.9(ABCB6):c.1663C>A(p.Gln555Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

ABCB6
ENST00000265316.9 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.85

Publications

5 publications found

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]

ABCB6 Gene-Disease associations (from GenCC):

dyschromatosis universalis hereditaria 3
Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
dyschromatosis universalis hereditaria
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial pseudohyperkalemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
microphthalmia, isolated, with coloboma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
microphthalmia, isolated, with coloboma 7
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ABCB6 links:

ENSG00000284820 (HGNC:):

ENSG00000284820 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.908

PP5

Variant 2-219213495-G-T is Pathogenic according to our data. Variant chr2-219213495-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 208249.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000265316.9. 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
	ABCB6	NM_005689.4	MANE Select	c.1663C>A	p.Gln555Lys	missense	Exon 11 of 19	NP_005680.1
	ABCB6	NM_001349828.2		c.1525C>A	p.Gln509Lys	missense	Exon 10 of 18	NP_001336757.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCB6	ENST00000265316.9	TSL:1 MANE Select	c.1663C>A	p.Gln555Lys	missense	Exon 11 of 19	ENSP00000265316.3
ENSG00000284820	ENST00000446716.5	TSL:2	n.*3622C>A		non_coding_transcript_exon	Exon 15 of 22	ENSP00000398528.1
ENSG00000284820	ENST00000446716.5	TSL:2	n.*3622C>A		3_prime_UTR	Exon 15 of 22	ENSP00000398528.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dyschromatosis universalis hereditaria 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Pathogenic

0.45

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.50

MetaRNN

Pathogenic

0.91

MetaSVM

Uncertain

0.74

MutationAssessor

Benign

1.0

PhyloP100

9.8

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.7

REVEL

Pathogenic

0.95

Sift

Benign

0.12

Sift4G

Benign

0.20

Polyphen

1.0

Vest4

0.95

MutPred

0.64

Gain of methylation at Q555 (P = 0.0121)

MVP

0.98

MPC

0.88

ClinPred

0.98

GERP RS

5.2

Varity_R

0.72

gMVP

0.96

Mutation Taster

=5/95

disease causing (ClinVar)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over