rs397514757

Positions:

• chr2-219218166-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_005689.4(ABCB6):​c.508A>G​(p.Ser170Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ABCB6 NM_005689.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.18

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]

ENSG00000284820 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-219218166-T-C is Pathogenic according to our data. Variant chr2-219218166-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 64647.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.2798796). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB6	NM_005689.4	c.508A>G	p.Ser170Gly	missense_variant	1/19	ENST00000265316.9	NP_005680.1
ABCB6	NM_001349828.2	c.508A>G	p.Ser170Gly	missense_variant	1/18		NP_001336757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB6	ENST00000265316.9	c.508A>G	p.Ser170Gly	missense_variant	1/19	1	NM_005689.4	ENSP00000265316.3
ENSG00000284820	ENST00000446716.5	n.*2281A>G		non_coding_transcript_exon_variant	6/22	2		ENSP00000398528.1
ENSG00000284820	ENST00000446716.5	n.*2281A>G		3_prime_UTR_variant	6/22	2		ENSP00000398528.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00420 Hom.: 1

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

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	0.24
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;.
Eigen	Benign	0.058
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Uncertain	-0.018	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.46
Sift	Benign	0.39	T;T
Sift4G	Benign	0.56	T;.
Polyphen		0.0010	B;B
Vest4		0.83
MutPred		0.36		Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);
MVP		0.93
MPC		0.19
ClinPred		0.97	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.54
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs397514757; hg19: chr2-220082888;