rs62453384

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000404938.7(ABCB5):​c.2429G>A​(p.Gly810Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000892 in 1,613,762 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: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

ABCB5
ENST00000404938.7 missense

Scores

5
9
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.44
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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.922

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCB5NM_001163941.2 linkuse as main transcriptc.2429G>A p.Gly810Asp missense_variant 21/28 ENST00000404938.7 NP_001157413.1
ABCB5NM_178559.6 linkuse as main transcriptc.1094G>A p.Gly365Asp missense_variant 12/19 NP_848654.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCB5ENST00000404938.7 linkuse as main transcriptc.2429G>A p.Gly810Asp missense_variant 21/281 NM_001163941.2 ENSP00000384881 P1Q2M3G0-4
ABCB5ENST00000258738.10 linkuse as main transcriptc.1094G>A p.Gly365Asp missense_variant 12/191 ENSP00000258738 Q2M3G0-1

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151930
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000123
AC:
31
AN:
251022
Hom.:
0
AF XY:
0.000155
AC XY:
21
AN XY:
135712
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000621
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000970
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000937
AC:
137
AN:
1461714
Hom.:
0
Cov.:
35
AF XY:
0.0000963
AC XY:
70
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000499
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000800
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152048
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000623
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00000428
Hom.:
14919
ExAC
AF:
0.000148
AC:
18
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.64
BayesDel_addAF
Benign
0.0026
T
BayesDel_noAF
Uncertain
0.13
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T;.
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.046
D
MetaRNN
Pathogenic
0.92
D;D
MetaSVM
Pathogenic
0.88
D
MutationAssessor
Uncertain
2.2
.;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-6.4
D;D
REVEL
Pathogenic
0.82
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.044
D;D
Vest4
0.59
MutPred
0.91
.;Loss of methylation at R367 (P = 0.0693);
MVP
0.95
MPC
0.034
ClinPred
0.67
D
GERP RS
3.8
Varity_R
0.80
gMVP
0.65

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs62453384; hg19: chr7-20762646; API