chr7-20643332-T-C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001163941.2(ABCB5):​c.463T>C​(p.Phe155Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,598 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: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ABCB5
NM_001163941.2 missense

Scores

6
10
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.82

Publications

5 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.96

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCB5NM_001163941.2 linkc.463T>C p.Phe155Leu missense_variant Exon 6 of 28 ENST00000404938.7 NP_001157413.1 Q2M3G0-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCB5ENST00000404938.7 linkc.463T>C p.Phe155Leu missense_variant Exon 6 of 28 1 NM_001163941.2 ENSP00000384881.2 Q2M3G0-4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000837
AC:
2
AN:
239010
AF XY:
0.0000153
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000185
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000275
AC:
4
AN:
1456598
Hom.:
0
Cov.:
31
AF XY:
0.00000276
AC XY:
2
AN XY:
724408
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33282
American (AMR)
AF:
0.00
AC:
0
AN:
43444
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26116
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39148
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86062
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52206
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
0.00000360
AC:
4
AN:
1110464
Other (OTH)
AF:
0.00
AC:
0
AN:
60118
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000166
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
D
M_CAP
Uncertain
0.094
D
MetaRNN
Pathogenic
0.96
D
MetaSVM
Uncertain
0.65
D
PhyloP100
7.8
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Pathogenic
0.86
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.0070
D
Vest4
0.71
MutPred
0.91
Loss of helix (P = 0.1706);
MVP
0.87
MPC
0.039
ClinPred
0.94
D
GERP RS
3.8
Varity_R
0.58
gMVP
0.60
Mutation Taster
=47/53
disease causing

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

Other links and lift over

dbSNP: rs77409024; hg19: chr7-20682955; API