NM_005689.4:c.2338G>T

Variant names:

• chr2-219210394-C-A
• rs201104967
• NM_005689.4:c.2338G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 5 publications found

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, MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• 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), G2P, ClinGen

ENSG00000284820 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005689.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB6	NM_005689.4	MANE Select	c.2338G>T	p.Val780Leu	missense	Exon 17 of 19	NP_005680.1	Q9NP58-1
	ABCB6	NM_001349828.2		c.2200G>T	p.Val734Leu	missense	Exon 16 of 18	NP_001336757.1	Q9NP58-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB6	ENST00000265316.9	TSL:1 MANE Select	c.2338G>T	p.Val780Leu	missense	Exon 17 of 19	ENSP00000265316.3	Q9NP58-1
	ENSG00000284820	ENST00000446716.5	TSL:2	n.*4122G>T		non_coding_transcript_exon	Exon 20 of 22	ENSP00000398528.1	H7C152
	ENSG00000284820	ENST00000446716.5	TSL:2	n.*4122G>T		3_prime_UTR	Exon 20 of 22	ENSP00000398528.1	H7C152

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	0.047	D
MutationAssessor	Benign	0.41	N
PhyloP100		2.2
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
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
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs201104967; hg19: chr2-220075116;