7-20723023-G-C

Variant summary

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

The NM_001163941.2(ABCB5):​c.2429G>C​(p.Gly810Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,714 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 š‘“: 6.8e-7 ( 0 hom. )

Consequence

ABCB5
NM_001163941.2 missense

Scores

4
8
7

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 rank MANE Protein UniProt
ABCB5NM_001163941.2 linkc.2429G>C p.Gly810Ala missense_variant Exon 21 of 28 ENST00000404938.7 NP_001157413.1 Q2M3G0-4
ABCB5NM_178559.6 linkc.1094G>C p.Gly365Ala missense_variant Exon 12 of 19 NP_848654.3 Q2M3G0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCB5ENST00000404938.7 linkc.2429G>C p.Gly810Ala missense_variant Exon 21 of 28 1 NM_001163941.2 ENSP00000384881.2 Q2M3G0-4
ABCB5ENST00000258738.10 linkc.1094G>C p.Gly365Ala missense_variant Exon 12 of 19 1 ENSP00000258738.6 Q2M3G0-1
ABCB5ENST00000441315.1 linkn.-71G>C upstream_gene_variant 2 ENSP00000398692.1 H7C165

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251022
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135712
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461714
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
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:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.044
T
BayesDel_noAF
Benign
-0.13
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;.
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Benign
0.028
D
MetaRNN
Pathogenic
0.92
D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Uncertain
2.8
.;M
PrimateAI
Benign
0.31
T
PROVEAN
Pathogenic
-5.5
D;D
REVEL
Pathogenic
0.76
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.0030
D;D
Vest4
0.40
MutPred
0.88
.;Loss of methylation at R367 (P = 0.1427);
MVP
0.94
MPC
0.025
ClinPred
0.98
D
GERP RS
3.8
Varity_R
0.56
gMVP
0.47

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