Variant 2-219213310-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_005689.4(ABCB6):c.1736G>A(p.Gly579Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ABCB6
NM_005689.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.71

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 links:

ENSG00000284820 (HGNC:):

ENSG00000284820 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-219213310-C-T is Pathogenic according to our data. Variant chr2-219213310-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 64648.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB6	NM_005689.4 linkuse as main transcript	c.1736G>A	p.Gly579Glu	missense_variant	12/19	ENST00000265316.9	NP_005680.1	Q9NP58-1
ABCB6	NM_001349828.2 linkuse as main transcript	c.1598G>A	p.Gly533Glu	missense_variant	11/18		NP_001336757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCB6	ENST00000265316.9 linkuse as main transcript	c.1736G>A	p.Gly579Glu	missense_variant	12/19	1	NM_005689.4	ENSP00000265316.3	Q9NP58-1
ENSG00000284820	ENST00000446716.5 linkuse as main transcript	n.*3695G>A		non_coding_transcript_exon_variant	16/22	2		ENSP00000398528.1	H7C152
ENSG00000284820	ENST00000446716.5 linkuse as main transcript	n.*3695G>A		3_prime_UTR_variant	16/22	2		ENSP00000398528.1	H7C152

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Dyschromatosis universalis hereditaria 3

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.

Eigen

Benign

0.019

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.57

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.26

T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

1.4

L;.

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.1

D;.

REVEL

Uncertain

0.36

Sift

Benign

0.039

D;.

Sift4G

Uncertain

0.043

D;.

Polyphen

0.57

P;B

Vest4

0.77

MutPred

0.48

Gain of solvent accessibility (P = 0.012);.;

MVP

0.86

MPC

0.28

ClinPred

0.94

GERP RS

4.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.7

Varity_R

0.34

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.66

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.66

Position offset: -23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over