rs1343501513

Variant names:

• chr12-122932206-C-A
• rs1343501513
• NM_019625.4:c.2026G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-122932206-C-A
• chr12-122932206-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019625.4(ABCB9):​c.2026G>T​(p.Glu676*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ABCB9 NM_019625.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.77
• Publications: 0 publications found

Genes affected

ABCB9 (HGNC:50): (ATP binding cassette subfamily B member 9) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This family member functions in the translocation of peptides from the cytosol into the lysosomal lumen. Alternative splicing of this gene results in distinct isoforms which are likely to have different substrate specificities. [provided by RefSeq, Jul 2011]

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_019625.4. 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
	ABCB9	NM_019625.4	MANE Select	c.2026G>T	p.Glu676*	stop_gained	Exon 11 of 12	NP_062571.1	Q9NP78-1
	ABCB9	NM_001437843.1		c.2026G>T	p.Glu676*	stop_gained	Exon 11 of 12	NP_001424772.1
	ABCB9	NM_001438398.1		c.1897G>T	p.Glu633*	stop_gained	Exon 10 of 11	NP_001425327.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB9	ENST00000280560.13	TSL:1 MANE Select	c.2026G>T	p.Glu676*	stop_gained	Exon 11 of 12	ENSP00000280560.8	Q9NP78-1
	ABCB9	ENST00000542678.5	TSL:1	c.2026G>T	p.Glu676*	stop_gained	Exon 11 of 12	ENSP00000440288.1	Q9NP78-1
	ABCB9	ENST00000442833.6	TSL:1	c.2026G>T	p.Glu676*	stop_gained	Exon 11 of 12	ENSP00000456375.1	Q9NP78-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400452 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690938

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31666

American (AMR) AF: 0.00 AC: 0 AN: 35882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25190

East Asian (EAS) AF: 0.00 AC: 0 AN: 35834

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079898

Other (OTH) AF: 0.00 AC: 0 AN: 58012

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	42
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		7.8
Vest4		0.74
GERP RS		4.5
Mutation Taster		=19/181	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1343501513; hg19: chr12-123416753;