7-20658647-A-T

Position:

• chr7-20658647-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001163941.2(ABCB5):​c.1678A>T​(p.Lys560Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCB5 NM_001163941.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.85

Genes affected

ABCB5 (HGNC:46): (ATP binding cassette subfamily B member 5) ABCB5 belongs to the ATP-binding cassette (ABC) transporter superfamily of integral membrane proteins. These proteins participate in ATP-dependent transmembrane transport of structurally diverse molecules ranging from small ions, sugars, and peptides to more complex organic molecules (Chen et al., 2005 [PubMed 15760339]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.1678A>T	p.Lys560Ter	stop_gained	14/28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.343A>T	p.Lys115Ter	stop_gained	5/19		NP_848654.3
ABCB5	NM_001163942.2	c.343A>T	p.Lys115Ter	stop_gained	5/6		NP_001157414.1
ABCB5	NM_001163993.3	c.343A>T	p.Lys115Ter	stop_gained	5/6		NP_001157465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1678A>T	p.Lys560Ter	stop_gained	14/28	1	NM_001163941.2	ENSP00000384881	P1
ABCB5	ENST00000258738.10	c.343A>T	p.Lys115Ter	stop_gained	5/19	1		ENSP00000258738
ABCB5	ENST00000443026.6	c.343A>T	p.Lys115Ter	stop_gained	5/6	1		ENSP00000406730
ABCB5	ENST00000406935.5	c.343A>T	p.Lys115Ter	stop_gained	5/6	2		ENSP00000383899

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	41
DANN	Uncertain	0.99
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
MutationTaster	Benign	1.1e-23	P;P;P;P
Vest4		0.76
GERP RS		4.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.24		Position offset: 29

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2301641; hg19: chr7-20698270;